Calixta, 30 mg 30 pcs

Mirtazapine is an antagonist of presynaptic α2-adrenoreceptors in the CNS and increases central noradrenergic and serotonergic transmission of nerve impulses. However, the enhancement of serotonergic transmission is realized only through serotonin 5-HT1 receptors, because mirtazapine blocks serotonin 5-HT2- and 5-HT3-receptors. Both enantiomers of mirtazapine are thought to have antidepressant activity, the S(+) enantiomer by blocking α2-adreno- and serotonin 5-NT2-receptors, the aR(-) enantiomer by blocking serotonin 5-NT3-receptors.

Mirtazapine’s sedative properties are due to its antagonistic activity toward H1-histamine receptors.

Mirtazapine is generally well tolerated. At therapeutic doses, it has almost no m-cholinergic effect and almost no effect on the cardiovascular system.

Pharmacokinetics

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

In the recommended dose range, the pharmacokinetic parameters of Mirtazapine have a linear dependence on the administered dose of the drug. Food intake has no effect on the pharmacokinetics of the drug. Mirtazapine is actively metabolized and excreted in the urine and feces within a few days. Its main pathways of 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-hydroxy metabolite Mirtazapine, while CYP3A4 presumably determines the formation of N-demethylated and N-oxidized metabolites.

Demethylmirtazapine is pharmacologically active.

The clearance of Mirtazapine is decreased in renal or hepatic insufficiency.

Indications

Depression.

Active ingredient

Composition

Active ingredient:

Associates:

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 dye (E172) – 0.1 mg, talc – 0.05 mg.

How to take, the dosage

The tablets should be taken orally with liquids if necessary, and swallowed without chewing.

Adults:

The effective daily dose is usually between 15 mg and 45 mg; the starting dose is 15 mg or 30 mg.

Elderly patients:

The recommended dose is the same as for adults. In elderly patients, dose increases should be made under the direct supervision of a physician in order to achieve a satisfactory and safe response to treatment.

Hepatic and renal disorders:

In patients with renal or hepatic impairment, the clearance of mirtazapine may be reduced. This should be considered when prescribing Calixta in this category of patients.

Calixta may be taken once daily, preferably at the same time, before bedtime. Calyxta may also be given twice a day, dividing the daily dose in half (once in the morning and once at night; the higher dose should be taken at night).

The treatment should be continued for 4-6 months, if possible, until the patient’s symptoms completely disappear. After that, treatment may be gradually withdrawn. Mirtazapine usually begins to exert its effects after 1 to 2 weeks of treatment. Treatment with an adequate dose should lead to a positive result after 2-4 weeks. If necessary, the dose may 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.

Interaction

Pharmacodynamic interaction

Mirtazapine should not be used in combination with MAO inhibitors or within two weeks after stopping treatment with an MAO inhibitor.

Mirtazapine may increase the sedative effects of benzodiazepines and other sedatives. Caution should be exercised when prescribing these medications with mirtazapine.

Mirtazapine may increase the depressant effects of alcohol on the CNS. Therefore, patients should be warned to avoid alcoholic beverages.

If other serotonergic medications (e.g., selective serotonin takeover inhibitors and venlafaxine) are used in combination with mirtazapine, there is a risk of interaction that may lead to serotonin syndrome.

Mirtazapine at a dose of 30 mg once daily caused a small but statistically significant increase in MHO (international normalized ratio) in subjects treated with warfarin. A more pronounced effect with a higher dose of mirtazapine cannot be excluded. It is recommended to monitor MHO in case of treatment with warfarin in combination with mirtazapine.

Mirtazapine is extensively metabolized with participation of CYP2D6 and CYP3A4 isoenzymes, and to a lesser extent with participation of CYP1A2 isoenzyme. Interaction studies in healthy volunteers have shown that paroxetine, a CYP2D6 isoenzyme inhibitor, has no effect on the pharmacokinetics of mirtazapine at equilibrium. Administration in combination with the potent CYP3A4 isoenzyme inhibitor, 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 CYP3A4 isoenzyme inhibitors, HIV protease inhibitors, azole antifungal drugs, erythromycin or nefazodone. Carbamazepine and phenytoin, CYP3A4 isoenzyme inducers, increased mirtazapine clearance approximately two-fold, resulting in 45-60% lower plasma concentrations of mirtazapine.

When carbamazepine or another microsomal liver enzyme inducer (e.g., rifampicin) is added to mirtazapine therapy, the dose of mirtazapine should be increased if necessary.

The dose of mirtazapine may need to be decreased when treatment with this medication is discontinued. When mirtazapine is used in combination with cimetidine, the bioavailability of mirtazapine may increase by more than 50%. The dose of mirtazapine should be decreased, if necessary, at the beginning of treatment in combination with cimetidine or increased when cimetidine treatment is stopped.

In in vivo interaction studies, mirtazapine had no effect on the pharmacokinetics of risperidone or paroxetine (CYP2D6 isoenzyme substrate), carbamazepine (CYP3A4 isoenzyme substrate), amitriptyline, cimetidine or phenytoin. No important clinical effects or changes in pharmacokinetics have been observed in humans when treated with mirtazapine in combination with lithium.

Special Instructions

When using Calixta, keep in mind:

– Worsening of psychotic symptoms may occur when using antidepressants to treat patients with schizophrenia or other psychotic disorders; paranoid ideas may increase.

– The depressive phase of manic-depressive psychosis may transform into a manic phase with treatment.

– In young adults (younger than 24 years) with depression and other psychiatric disorders, antidepressants, compared with placebo, increase the risk of suicidal ideation and suicidal behavior. Therefore, when prescribing Calixta in young adults (younger than 24 years), the risk of suicide and the benefits of the medication should be weighed against each other. In short-term studies, people over 24 years of age had no increased risk of suicide, and people over 65 years of age had a slightly decreased risk of suicide. Any depressive disorder itself increases the risk of suicide. Therefore, the patient should be monitored during treatment to detect abnormalities or behavioral changes as well as suicidal tendencies.

While Calixta is not addictive, post-registration experience has shown that abrupt discontinuation of treatment after prolonged use can sometimes cause withdrawal symptoms. Most withdrawal reactions are mild and self-limiting. The most commonly reported withdrawal symptoms were dizziness, agitation, anxiety, headache, and nausea. Although these have been reported as withdrawal symptoms, it should be understood that these symptoms may be related to the underlying disease. It is recommended that treatment with mirtazapine be discontinued gradually.

– Elderly patients tend to be more sensitive, especially with regard to side effects. In clinical trials of Calixta, side effects have not been observed to be more frequent in elderly patients than in other age groups, but they may be more severe, but data are still limited.

– Treatment should be discontinued if signs of jaundice occur.

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

– Depression of bone marrow function, usually appearing as granulocytopenia or agranulocytosis, is rarely seen with Calixta. It occurs mostly after 4-6 weeks of treatment and is reversible after discontinuation of treatment. The physician should be alert for symptoms such as fever, sore throat, stomatitis, and other flu-like symptoms and inform the patient; if these symptoms occur, treatment should be stopped and blood tests performed.

Influence on driving and operating ability

The drug Calixta may decrease concentration. During treatment with antidepressants, patients should avoid potentially hazardous activities requiring high psychomotor reactions, such as driving or operating machinery.

Contraindications

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

– Hypersensitivity to mirtazapine or any of the excipients;

Since the safety and effectiveness of Calixta has not been established for children, the use of Calixta for treatment of children under 18 years is not recommended.

Cautions:

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

– acute closed-angle glaucoma and elevated intraocular pressure;

– diabetes mellitus;

– urinary disorders, including.in prostatic hyperplasia;

– concomitant use of benzodiazepines with the drug Calixta.

Correction of the dosage regimen and regular medical monitoring are necessary for the following categories of patients:

– patients with epilepsy and organic brain lesions (against the background of therapy with the drug Calixta in rare cases, the development of seizures is possible);

– patients with hepatic or renal insufficiency;

Patients with heart disease (conduction disorders, angina, or recent myocardial infarction);

Patients with cerebrovascular disease (including coronary artery disease).

Patients with cerebrovascular disease (including history of ischemic stroke);

Patients with arterial hypotension and conditions predisposing to arterial hypotension (including

Patients with dehydration and hypovolemia;

Patients who abuse medications, with dependence on drugs affecting the CNS, with mania, hypomania.

Side effects

Gastrointestinal disorders:very common – dry mouth; common – nausea, diarrhea, vomiting; infrequent – decreased sensitivity of the oral mucosa; frequency is not determined – swelling of the oral mucosa.

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

Nervous system disorders: very common – somnolence (which may lead to impaired concentration), usually occurring during the first weeks of treatment. (N.B. dose reduction usually does not lead to less sedation, but may reduce 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, oral mucosal paresthesias.

Skin and subcutaneous tissue: frequently – skin rash.

Skeletal-muscular system and connective tissue: frequently – arthralgia, myalgia, back pain.

From the endocrine system: frequency not established – impaired secretion of antidiuretic hormone.

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

Cardiovascular system disorders:often – orthostatic hypotension; infrequently – decreased BP.

General disorders and disorders at the site of administration:often – local edema; infrequently – fatigue.

Hepatic and biliary tract disorders:frequently – increased serum transaminase activity.

Psychiatric disorders: frequent – unusual dreams, confusion, anxiety*, insomnia*, infrequent – nightmares, mania, agitation, hallucinations, psychomotor agitation (including agitation and hyperkinesia); frequency not determined – suicidal ideas, suicidal behavior. * Usually with antidepressant treatment, anxiety and insomnia, which may be symptoms of depression, may develop or worsen.

In treatment with Calixta, the development or worsening of anxiety and insomnia has very rarely been reported.

Overdose

In case of overdose, symptomatic therapy should be given to support vital body functions.

Active charcoal or gastric lavage should be administered. Available experience regarding overdose with Calixta alone indicates that symptoms are usually mild. CNS depression has been reported, with disorientation and prolonged sedation combined with tachycardia and a mild rise or fall in BP.

But there is a possibility of more severe results (including death) when doses are much higher than the therapeutic dose, especially when overdosed with multiple drugs taken simultaneously.

Pregnancy use

The safety of the drug Calixta in pregnancy in humans has not been established, but no teratogenic effect was found in animals, so the drug may be used during pregnancy only when the benefit to the mother exceeds the potential risk to the fetus.

The use of the drug Calixta during lactation is not recommended because of the lack of data on its excretion with breast milk in humans.

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