Kaliksta - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate - 44,40 / 88,80 / 133,20 mg, corn starch - 28,00 / 56,00 / 84,00 mg, giprolose - 15,00 / 30,00 / 45,00 mg, microcrystalline cellulose - 15,00 / 30,00 / 45,00 mg, pregelatinized starch - 15,00 / 30,00 / 45,00 mg, talc - 1,40 / 2,80 / 4,20 mg, magnesium stearate - 0,70 / 1.40 / 2.10 mg, silicon dioxide - 0.50 / 1.00 / 1.50 mg; tablet shell: hypromellose-5 CPS - 2.40 / 4.80 / 7.20 mg, macrogol 6000 - 0.20 / 0.40 / 0.60 mg, titanium dioxide 0.25 / 0.50 / 1.05 mg, dye iron oxide yellow (E 172) (for dosages of 15 mg and 30 mg) - 0.10 / 0.15 mg, iron dye red oxide (E 172) (for a dosage of 30 mg) - 0.05 mg, talc - 0.05 / 0.10 / 0.15 mg.

Description:

15 mg: Oblong tablets covered with a film coating of yellow color with a risk on one side.

30 mg: Oblong tablets covered with a film coat of a brownish-pink color with a risk on one side.

45 mg: Oblong tablets covered with a film coating of white color.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.X.11 Mirtazapine

Pharmacodynamics:

Pharmacological properties

Kaliksta® is a tetracyclic antidepressant with predominantly sedative effect. The drug is most effective in depressive states with presence in the clinical picture of such symptoms as inability to test pleasureand 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. The antidepressant effect of Kalikst® usually comes after 1-2 weeks of treatment.

Pharmacodynamics

Mirtazapine is an antagonist of presynaptic α₂adrenoreceptors in the central nervous system and enhances central noradrenergic and serotonergic transmission of nerve impulses.In this case, the enhancement of serotonergic transmission is realized only through serotonin 5-HT₁-receptors, since mirtazapine blocks serotonin 5-HT₂ and 5-HT₃-receptors. It is believed that both enantiomers of mirtazapine have antidepressant activity, S (+) enantiomer-blockingα₂-adreno- and serotonin 5-HT₂-receptors, and R (-) enantiomer-blocking serotonin 5-HT₃-receptors.

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 has almost no m-cholin blocking effect and practically no effect on the cardiovascular system.

Pharmacokinetics:

After oral administration, the drug mirtazapine quickly absorbed (bioavailability of about 50%), reaching a maximum concentration in the blood plasma after about 2 hours. About 85% of mirtazapine binds to plasma proteins. The average half-life is between 20 and 40 hours (rarely up to 65 hours). A shorter half-life 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 It 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) participate in the formation of 8-hydroxymetabolite mirtazapine, while CYP3A4 presumably determines education N-detylated and Noxidized metabolites. Demethylmirtazapine is pharmacologically active. The clearance of mirtazapine decreases with renal or hepatic insufficiency.

Indications:

Depression.

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, Kalikst® preparation should not be prescribed.

Since the safety and efficacy of Kalikst® for children are not established, it is not recommended to use Kalikst® for children under 18 years of age.

Carefully:

Correction of the dosing regimen and regular medical control are necessary for the following categories of patients:

- patients with epilepsy and organic lesions of the brain (on the background of therapy with Kaliksta in rare cases, the development of seizures);

- patients with hepatic or renal insufficiency;

- patients with heart disease (conduction disorder, 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 arterial hypotension (including with dehydration and hypovolemia);

- patients abusing drugs, with dependence on drugs that affect the central nervous system, with mania, hypomania.

Like other antidepressants, Kalikst® 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;

- while simultaneous use of benzodiazepines with Kalikst®.

Pregnancy and lactation:

The safety of Kalikst® in pregnancy has not been established in humans, however, there is no teratogenic effect 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 Kaliksta during lactation is not recommended because of the lack of data on its excretion in human milk.

Dosing and Administration:

Tablets should be taken orally, if necessary, washed down with liquid, 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 physician.

Dysfunction of the liver and kidneys:

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

Kaliksta ® can be taken once a day, preferably at the same time, before bedtime. Kaliksta ® can also be prescribed for reception 2 times a day, dividing the daily dose in half (once in the morning and once a night, a higher dose should be taken at night).

Treatment should, if possible, continue for 4-6 months until the symptoms disappear completely. After this treatment can be gradually canceled. Mirtazapine usually begins 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). In the absence of positive dynamics of treatment, after 2-4 weeks treatment should be discontinued.

Side effects:

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: Often (≥1/10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10000 and <1/1000), frequency is not set (<1/10000)

On the part of the blood and lymphatic system: frequency not established - bone marrow suppression (granulocytopenia, agranulocytosis, aplastic anemia and thrombocytopenia), eosinophilia.

From the nervous system: Often - drowsiness (which can lead to impaired concentration), usually occurring during the first weeks of treatment (N.B. lowering 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; rarely - convulsions (stroke), serotonin syndrome, paresthesia of the oral mucosa.

From the gastrointestinal tract: Often - dry mouth; often - nausea, diarrhea, vomiting; infrequently - decreased sensitivity of the oral mucosa; frequency not set - edema of the oral mucosa.

Co hand skin and subcutaneous tissue: often - skin rash.

From the musculoskeletal system and connective tissue: often - Arthralgia, myalgia, back pain.

Co hand endocrine system: frequency is not set - violation of the secretion of antidiuretic hormone.

Co hand metabolism and nutrition: Often - increased appetite.

Co hand of cardio-vascular system: often - Orthostatic hypotension; infrequently - lowering blood pressure.

General disorders and disorders at the site of administration: often - Local edema; infrequently - fatigue.

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

Disorders of the psyche: often - unusual dreams, confusion, anxiety *, insomnia *; infrequently - nightmares, mania, agitation, hallucinations, psychomotor agitation (including acacia and hyperkinesia); frequency not set - suicidal ideation, suicidal behavior.

* usually with the treatment of antidepressants, anxiety and insomnia, which may be symptoms of depression, may develop or worsen. The treatment with Kaliksta was very rarely reported on the development or worsening of anxiety and insomnia.

Overdose:

The experience with an overdose of Kaliksta alone indicates that the symptoms are usually mild.It was reported that the central nervous system was depressed, accompanied by disorientation and a prolonged sedative effect 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 when overdosed with several drugs taken simultaneously.

In case of an overdose, symptomatic therapy should be used to maintain the vital functions of the body. You should enter Activated carbon or rinse the stomach.

Interaction:

Pharmacokinetic interaction

Mirtazapine is extensively metabolized with the participation of isoenzymes CYP2D6 and CYP3A4 and, to a lesser extent, involving isoenzyme CYP1A2. The study of interaction in healthy volunteers showed that paroxetine, inhibitor of isoenzyme CYP2D6, does not affect the pharmacokinetics of mirtazapine in the equilibrium state. Introduction in combination with a potent inhibitor of isoenzyme CYP3A4, ketoconazole increased the maximum concentration in plasma and AUC (area under the curve of dependence of the time) of mirtazapine by approximately 40% and 50%, respectively.

Caution should be exercised when using mirtazapine in combination with potent inhibitors of isoenzyme CYP3A4, HIV protease inhibitors, azole antifungal drugs, erythromycin or nefazodone.

Carbamazepine and phenytoin, isoenzyme inducers CYP3A4, increased the clearance of mirtazapine approximately twice, which resulted in a 45-60% decrease in the concentrations of mirtazapine in plasma. When adding carbamazepine or other inducer of microsomal liver enzymes (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 applying mirtazapine in combination with cimetidine bioavailability of mirtazapine can 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 upon discontinuation treatment with cimetidine.

In studies on the interaction in vivo, mirtazapine did not provide effects 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 can 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 the use of other serotonergic drugs (for example, selective inhibitors of serotonin and venlafaxine seizure) 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 once a day caused a small but statistically significant increase in INR (an international normalized ratio) in subjects treated with warfarin. It is impossible to exclude a more pronounced effect with a higher dose mirtazapine. It is recommended to monitor INR in case of treatment with warfarin in combination with mirtazapine.

Special instructions:

When using Kaliksta, one should keep in mind:

- Deterioration of psychotic symptoms may 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 against 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 appointing Kaliksta 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 older than 65 years - slightly decreased. 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.

- Despite the fact that Kaliksta® preparation is not addictive, based on the post-experience 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 trials of Kaliksta, it was not observed that side effects are more frequent in elderly patients 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 during treatment with Kalikst®.

- Oppression of bone marrow functions, usually appearing in the form of granulocytopenia or agranulocytosis, is rarely observed with the use of Kalikst®. Appears mostly after 4-6 weeks of treatment and reversibly after discontinuation of treatment. The doctor should carefully consider symptoms such as fever, sore throat, stomatitis, and other signs of flu-like syndrome and inform the patient about it, if such symptoms appear, stop treatment and make a blood test.

Effect on the ability to drive transp. cf. and fur:

Kaliksta ® can reduce concentration. 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.

Form release / dosage:

Film-coated tablets, 15 mg, 30 mg and 45 mg.

Packaging:

15 mg: For 30 tablets, film-coated in Al / PVC / PVDC blister.One blister, along with instructions for use, is placed in a cardboard box.

30 mg and 45 mg: For 15 tablets, film-coated in Al / PVC / PVDC blister. Two blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001110

Date of registration:03.11.2011

Expiration Date:03.11.2016

The owner of the registration certificate:Beluga, medicines and cosmetics.Beluga, medicines and cosmetics. Croatia

Manufacturer: & nbsp

BELUPO, Pharmaceuticals & Cosmetics, d.d. Croatia

Representation: & nbspBeluga, medicines and cosmetics. Beluga, medicines and cosmetics. Croatia

Information update date: & nbsp05.09.2016

Illustrated instructions

Instructions

Kaliksta® (Calixta®)