medicalmeds.eu Medicines Antidepressants. Kaliksta

Kaliksta

Producer: BELUPO, Pharmaceuticals & Cosmetics, d.d. Republic of Croatia

Code of automatic telephone exchange: N06AX11

Release form: Firm dosage forms. Tablets.

Indications to use: Depression.

General characteristics. Structure:

Active agent: миртазапин 15 mg; 30 mg; 45 mg

Excipients: lactoses monohydrate — 44,4/88,8/133,2 mg, starch corn — 8/56/84 mg, a hypro rod — 15/30/45 mg, MKTs — 15/30/45 mg, starch prezhelatinizirovanny — 15/30/45 mg, talc — 1,4/2,8/4,2 mg, magnesium stearate — 0,7/1,4 / 2,1 mg, silicon dioxide — 0,5/1/1,5 mg

The cover is film: gipromelloza-5 CPS — 2,4/4,8/7,2 mg, a macrogoal 6000 — 0,2/0,4 / 0,6 mg, titanium dioxide — 0,25/0,5/1,05 mg, dye ferrous oxide yellow (E172) (for dosages of 15 mg and 30 mg) — 0,1/0,15 mg, dye ferrous oxide red (E172) (for a dosage of 30 mg) — 0,05 mg, talc — 0,05/0,1/0,15 mg.

Pharmacological properties:

Drug is tetracyclic antidepressant with preferential sedative action. Drug is most effective at depressions with existence. in a clinical picture of such symptoms, as inability to feel pleasure and joy, interest loss (angedoniya), psychomotor block, sleep disorders (especially in the form of early awakenings) and loss, weight, and also other symptoms: suicide thoughts and daily mood swings. The antidepressive effect of drug usually occurs in 1-2 weeks of treatment. Pharmacodynamics. Mirtazapin is an antagonist of presynaptic alfa2-adrsnoretseptor in the central nervous system and strengthens the central noradrenergichesky and serotonergic transfer, nervous impulses. At the same time strengthening of serotonergic transfer is implemented only through serotoninovy 5-HT1-retseptory as миртазапин blocks serotoninovy 5-HT2 and 5-HT3-retseptory. It is considered that both enantiomer of a mirtazapin possess. antidepressive activity, S (+) an enantiomer - blocking alfa2-adreno-and serotoninovy 5-HT2-retseptory, a R (-) an enantiomer - blocking serotoninovy, 5-NTZ-receptors. Sedative properties of a mirtazapin are caused by its antagonistic activity in relation to H1 - histamine receptors. Mirtazapin is usually well had. In therapeutic doses practically does not render m - the cholineblocking action and practically does not influence cardiovascular system. Pharmacokinetics. After a peroral priyema.preparat миртазапин it is quickly soaked up, (bioavailability about 50%), reaching the maximum concentration in a blood plasma approximately in 2 h. About 85% of a mirtazapin contact proteins of plasma. The average elimination half-life makes from 20 to 40 h (seldom to 65 h). Shorter elimination half-life is observed at young people. Equilibrium concentration of substance is reached in 3-4 days and further it does not change. In the recommended range of doses pharmacokinetic indicators of a mirtazapin have linear dependence on the entered drug dose. Meal does not exert impact on drug pharmacokinetics. Mirtazapin is actively metabolized and brought with urine and a stake within several days. The main ways of his metabolism in an organism are demethylation and oxidation with the subsequent conjugation. Isoenzymes of P450 cytochrome (CYP2D6 and CYP1A2) participate in education 8 hydroxymetabolites of a mirtazapin while CYP3A4 presumably defines formation of N-demetilirovannykh and the N-oxidized metabolites. Demetilmirtazapin pharmacological is active. The clearance of a mirtazapin decreases at a renal or liver failure.

Indications to use:

Depression.

Route of administration and doses:

Inside, if necessary washing down with liquid, to swallow, without chewing.
Adults. The effective daily dose usually is between 15 and 45 mg; the initial dose makes 15 or 30 mg.

Elderly patients. The same recommended dose, as for adults. At elderly patients to achieve the satisfactory and safe response to treatment, increase in a dose it is necessary to make under direct observation of the doctor.

Abnormal liver function and kidneys. At patients with a renal or liver failure the clearance of a mirtazapin can be reduced. It should be considered at purpose of the drug Kaliksta® of this category of patients.

It is possible to accept the drug Kaliksta® 1 time a day, more preferably at the same time, before going to bed. It is also possible to appoint the drug Kaliksta® for reception 2 times a day, having divided a daily dose in half (once in the morning and once for the night, higher dose should be accepted for the night).

Treatment should be continued whenever possible within 4–6 months before total disappearance of symptoms at the patient. After that treatment can be cancelled gradually. Mirtazapin begins to have the effect usually after 1–2 weeks of treatment. Treatment by an adequate dose has to lead to a positive take in 2–4 weeks. If necessary the dose can be increased to maximum (45 mg). In case of lack of positive dynamics of treatment in 2–4 weeks treatment should be stopped.

Features of use:

At drug use, it must be kept in mind: deterioration in psychotic symptoms can happen at use of antidepressants for treatment of patients to schizophrenia or other psychotic disturbances; the paranoid ideas can amplify. The depressive phase of maniac-depressive psychosis against the background of treatment can be transformed to a maniacal phase. At young people (24 years are younger) with a depression and other mental disturbances, antidepressants, in comparison with placebo, increase risk of emergence of suicide thoughts and suicide behavior. Therefore at purpose of drug at young people (24 years are younger) it is necessary to correlate risk of a suicide and advantage of drug use. In short-term researches at people 24 years are more senior the risk of a suicide did not increase, and at people 65 years are more senior - decreased a little. Any depressive frustration in itself increases risk of a suicide. Therefore during treatment for the patient observation for the purpose of identification of disturbances or changes of behavior, and also suicide bents has to be established. In spite of the fact that drug does not cause accustoming, proceeding their post-registration experience it turned out that the sharp termination of treatment after long use can sometimes become the reason of symptoms of cancellation. The majority of reactions of cancellation are weak and self-limited. It was most often reported about the following symptoms of cancellation: dizziness, agitation, alarm, headache and nausea. Though about them it was reported as about cancellation symptoms, it is necessary to understand that these symptoms can be connected with a basic disease. It is recommended to stop treatment mirtazapiny gradually. Patients of advanced age are usually more sensitive, especially concerning side effects. In clinical trials of drug it was not noted that at patients of advanced age side effects happen more often than in other age groups, but they can be more expressed, however data are still limited. At emergence of symptoms of jaundice treatment should be stopped. The patient recommend to avoid use of alcohol at treatment by drug. The oppression of functions of marrow which is usually appearing in the form of a granulocytopenia or an agranulocytosis is seldom observed at drug use. Appears mostly after 4-6 weeks of treatment and it is reversible after the termination treatment. The doctor should show consideration for such symptoms as fervescence, pharyngalgias, stomatitis, and other signs of a grippopodobny syndrome and to inform on it the patient; at emergence of similar symptoms it is necessary to stop treatment and to make blood test. Influence on ability of control of vehicles of N of mechanisms. Drug can reduce concentration of attention. In the course of treatment by antidepressants patients should avoid performance of potentially dangerous types of activity demanding the high speed of psychomotor reactions, such as driving of the car or control of mechanisms.

Side effects:

At patients with a depression a number of the symptoms caused by a disease therefore it is sometimes difficult to distinguish the symptoms connected with a disease and the symptoms caused by drug use is observed. From blood and lymphatic system: frequency is not established - oppression of marrow (a granulocytopenia, агралулоцитоз, aplastic anemia and thrombocytopenia), an eosinophilia. From a nervous system: very often - the drowsiness (which can bring to the broken concentration of attention) which is usually arising within the first weeks of treatment. (N.B. the dose decline usually does not lead to smaller sedation, but can reduce efficiency of antidepressant), sedation, a headache; often - a lethargy, dizziness, a tremor; infrequently - paresthesia, a syndrome of "uneasy legs", a syncope; seldom - a myoclonus, it is very rare - spasms (stroke), a serotoiinovy syndrome, paresthesias of a mucous membrane of an oral cavity. From digestive tract: very often - dryness in a mouth; often - nausea, diarrhea, vomiting; infrequently - decrease in sensitivity of a mucous membrane of an oral cavity; frequency is not established - hypostasis of a mucous membrane of an oral cavity. From skin and hypodermic fabrics: often — skin rash. From skeletal and muscular system and connecting fabric: often — an arthralgia, a mialgiya, a dorsodynia. From endocrine system: frequency is not established - disturbance of secretion of antidiuretic hormone. Co of the party of a metabolism and food: very often - the increased appetite. From cardiovascular system: often - ortostatichssky hypotension; infrequently - a lowering of arterial pressure. The general frustration and disturbances in an injection site: often - local swelled; infrequently - fatigue. From a liver and biliary tract: seldom - increase in activity of transaminases of serum. Disturbances of mentality: often - unusual dreams, confusion of consciousness, alarm, sleeplessness, infrequently - nightmares, a mania, agitation, hallucinations, psychomotor excitement (including an akataziya and a hyperkinesia); frequency is not established — the suicide ideas, suicide behavior. Usually at treatment by antidepressants the alarm and sleeplessness which can be depression symptoms can develop or worsen. At treatment by drug about development or deterioration alarm and sleeplessnesses it was reported very seldom.

Interaction with other medicines:

Pharmacokinetic interaction. Mirtazapin is intensively metabolized with participation of isoenzymes of CYP2D6 and CYP3A4, and to a lesser extent with participation of an isoenzyme of CYP1A2. Studying of interaction at healthy volunteers showed that пароксетин, CYP2D6 isoenzyme inhibitor, does not exert impact on pharmacokinetics of a mirtazapin at an equilibrium state. Introduction in combination with powerful inhibitor of an isoenzyme CYP3A4, ketokonazoly increased the maximum concentration in plasma and AUC (the area under a curve of dependence of concentration from time) a mirtazapina approximately for 40% and 50% respectively. It is necessary to show care at use of a mirtazapin in combination with powerful inhibitors of an isoenzyme CYP3A4, HIV protease inhibitors, azolny antifungal medicines, erythromycin or nefazodony. Carbamazepine and Phenytoinum, CYP3A4 isoenzyme inductors, increased clearance of a mirtazapin approximately twice that led to 45-60% to decrease in concentration of a mirtazapin - century to plasma. At addition of carbamazepine or other inductor of microsomal enzymes of a liver (for example, rifampicin) to therapy mirtazapiny, the dose of a mirtazapin if necessary should be increased. At the treatment termination need of a dose decline of a mirtazapin can arise such medicine. At use of a mirtazapin in combination with tsimstidiny bioavailability of a mirtazapin can increase more than by 50%. The dose of a mirtazapin if necessary should be reduced in an initiation of treatment in combination with Cimetidinum or to increase at the treatment termination by Cimetidinum. In the researches on studying of interactions conducted by in vivo миртазапин did not exert impact on pharmacokinetics of a risperidon or a paroksetin (CYP2D6 isoenzyme substrate), carbamazepine (CYP3A4 isoenzyme substrate), amitriptyline, Cimetidinum or Phenytoinum. Important clinical effects or changes of a pharmakokiiyetika at the person at treatment were not observed mirtazapiny in combination with lithium. Pharmakodinamichesky interaction. Mirtazapin it is not necessary to apply in combination with MAO inhibitors or within two weeks after the treatment termination by MAO inhibitor. Mirtazapin can increase sedative properties of benzodiazepines and other sedatives. It is necessary to show care at purpose of these medicines together with mirtazapiny. Mirtazapin can strengthen depressive effect of alcohol on TsNS. Therefore patients have to be warned about need to avoid the use of alcoholic drinks. In case of use of other serotonergic medicines (for example, the selection inhibitors of serotonin reuptake and a venlafaksin) in combination with mirtazapiny, there is a risk of interaction which can lead to development of a serotoninovy syndrome. Mirtazapin in a dose of 30 mg caused small, but statistically reliable increase in MHO (the international normalized relation) in subjects once a day; receiving treatment by warfarin. It is impossible to exclude more expressed effect at higher dose of a mirtazapin. It is recommended to control MHO in case of treatment by warfarin in combination with mirtazapiny.

Contraindications:

Hypersensitivity to a mirtazapin or to any of excipients. The patient with such rare hereditary problems as a lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption, drug it is not necessary to appoint. As safety and efficiency of drug for children's age are not established, it is not recommended to use drug for treatment of children up to 18 years. With care. Correction of the mode of dosing and regular medical control are necessary for the following categories of patients: patients with epilepsy and organic lesions of a brain (against the background of therapy by drug development of spasms is in rare instances possible); patients with a liver or renal failure; patients with heart diseases (conductivity disturbance, stenocardia or recently postponed myocardial infarction); patients with cerebrovascular diseases (including with an ischemic stroke in the anamnesis); patients with arterial hypotension and with the states contributing to arterial hypotension (including with dehydration and a hypovolemia); the patients abusing medicines with dependence on the medicines influencing the central nervous system with manias, hypomanias. As well as it is necessary to use other antidepressants, drug with care in the following cases: disturbance of an urination, including at a prostate hyperplasia; acute closed-angle glaucoma and the increased intraocular pressure; diabetes mellitus; at simultaneous use of benzodiazepines with drug. Use at pregnancy and in the period of a lactation. Safety of use of drug at pregnancy at the person is not established, however at animals of teratogenic effect is not revealed therefore drug can be used during pregnancy only in that case when the advantage for mother exceeds potential risk for a fruit. Use of drug in the period of a lactation is not recommended due to the lack of data on its removal with breast milk at the person.

Overdose:

The available experience concerning overdose only indicates by drug that symptoms usually happen weak. It was reported about the oppression of the central nervous system which was followed by a disorientation and long sedation in combination with tachycardia and weak increase or a lowering of arterial pressure. However there is a probability of heavier results (including a lethal outcome) at the doses much exceeding a therapeutic dose in particular at overdoses by several drugs accepted at the same time in case of overdose symptomatic therapy for maintenance of the vital functions of an organism has to be carried out. It is necessary to enter absorbent carbon or to wash out a stomach.