Kvetiapin

General characteristics. Structure:

Active agents: the kvetiapina fumarates (a kvetiapina гемифумарат), in terms of кветиапин 25 mg, 100 mg, 200 mg and 300 mg;

excipients: hypro rod (hydroxypropyl cellulose Klutsel LF), hydrophosphate calcium dihydrate, starch prezhelatinirovanny, magnesium stearate, sodium carboxymethylstarch (sodium starch glycollate; примогель), cellulose microcrystallic;

structure of a film cover: АкваПолиш®D 8107 [a gipromelloza (gidroksipropilmetit cellulose), глицерол (glycerin), cellulose microcrystallic, talc, dye кандурин silver gloss ([potassium E555 aluminosilicate, E171 dioxide titanium]), an aluminum varnish on the basis of dye indigo carmine].

Description

Tablets, film coated blue color with nacreous gloss, round, biconvex. On cross section two layers are visible; internal — white color.

Pharmacological properties:

Pharmacodynamics. Antipsychotic means (neuroleptic). Shows higher affinity to receptors of serotonin (5-HT2), than to receptors of D1 and D2 dopamine in a brain. Has tropism to histamine and to alfa1-adrenoceptors, is less active in relation to alfa2-adrenoceptors. Elective affinity is not revealed to
m-holino-and to benzodiazepine receptors. Reduces activity of mesolimbic A10-dofaminergichesky neurons, in comparison with A9-nigrostriatnymi the neurons involved in motive functions. Does not cause long increase in concentration of prolactin. Communication duration with 5-HT2-serotoninovymi and D2-dofami-new receptors makes less than 12 h.

Pharmacokinetics. Absorption — high, meal does not influence bioavailability. Communication with proteins of plasma — 83%. It is actively metabolized in a liver with formation pharmacological of inactive metabolites under the influence of an isoenzyme of CYP3A4 mediated by P450 cytochrome. Kvetiapin and some of his metabolites possess a weak inhibiting effect on isoenzymes of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 cytochrome, but only in concentration, at 10-50 times exceeding those which arise at usually used dose — 300–450 mg/days.

It is removed by kidneys of 73%, through intestines — 21%. An elimination half-life — 7 h. The average clearance at elderly patients is 30-50% less, than observed at patients aged from 18 up to 65 years. At a renal and liver failure the clearance decreases by 25%.

Indications to use:

- acute and chronic psychoses (including at schizophrenia);

Yo-maniacal episodes in structure of bipolar disorder.

Route of administration and doses:

Inside, 2 times a day, irrespective of meal.

Treatment of acute and chronic psychoses, including schizophrenia.

Daily dose for the first 4 days of therapy — 50 mg (1 day), 100 mg (2 day), 200 mg (3 day), 300 mg (4 day). Since 4 days, the dose has to be titrated to effective, ranging from 300 to 450 mg/days, if necessary — to 750 mg/days.

Treatment of maniacal episodes in structure of bipolar disorder.

Kvetiapin is applied as monotherapy or as adjuvant therapy to stabilization of mood.

Daily dose for the first 4 days of therapy — 100 mg (1 day), 200 mg (2 day), 300 mg
(3 day), 400 mg (4 day). Further by 6th day of therapy the daily dose of drug can be increased to 800 mg. Increase in a daily dose should not exceed 200 mg a day.

Depending on clinical effect and individual portability, the dose can vary ranging from 200 to 800 mg/days. Usually effective dose makes from 400 to 800 mg/days.

For treatment of schizophrenia the maximum recommended daily dose of a kvetiapin makes 750 mg, for treatment of maniacal episodes in structure of bipolar disorder the maximum recommended daily dose of a kvetiapin makes 800 mg/days.

At a renal and/or liver failure and elderly patients have an initial dose — 25 mg/days, with the subsequent daily increase by 25–50 mg before achievement of an effective dose.

Features of use:

The interrelation between reception of a kvetiapin and increase in a QTc-interval is not revealed. However, at use of a kvetiapin along with the drugs extending QTS interval it is necessary to be careful.

At children, teenagers and young people (24 years are younger) with a depression, other mental disturbances antidepressants, in comparison with placebo, increase risk of emergence of suicide thoughts and suicide behavior. Therefore at prescription of antidepressants at children, teenagers and young people (24 years are younger) it is necessary to correlate risk of a suicide and advantage of their 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 by antidepressants for all patients observation for the purpose of early identification of disturbances or changes of behavior, and also suicide bents has to be established.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From a nervous system: drowsiness, dizziness, a headache, uneasiness, an adynamy, hostility, excitement, sleeplessness, an akathisia, a tremor, spasms, a depression, paresthesias, a malignant antipsychotic syndrome (a hyperthermia, muscular rigidity, the changed mental status, lability of the autonomic nervous system, increase in activity of a kreatinfosfokinaza).

From cardiovascular system: the orthostatic hypotension (which is followed by dizziness), tachycardia, a faint, lengthening of an interval of QT (the interrelation of use of a kvetiapin with continuous increase in QTc is not revealed).

From the alimentary system: dryness of a mucous membrane of an oral cavity, nausea, vomiting, abdominal pain, diarrhea or lock, increase in activity of "hepatic" transaminases.

From respiratory system: pharyngitis, rhinitis.

Allergic reactions: skin rash, eosinophilia.

Laboratory indicators: leukopenia, hypercholesterolemia, gipertriglitseridemiya, decrease in concentration of thyroxine (first 4 weeks).

Others: a back pain, thorax pain, subfebrile condition, increase in body weight (it is preferential in the first weeks of treatment), a mialgiya, a xeroderma, sight easing.

At prolonged use of a kvetiapin there is potentiality of development of late dyskinesia. At emergence of symptoms of late dyskinesia it is necessary to reduce a dose or to stop further treatment kvetiapiny.

At sharp cancellation of high doses of antipsychotic drugs the following acute reactions (a syndrome of "cancellation") — nausea, vomiting, seldom sleeplessness can be observed. It was reported about cases of an aggravation of psychotic symptoms and emergence of involuntary motive frustration (an akathisia, dystonia, dyskinesia). In this connection, drug withdrawal is recommended to be carried out gradually.

Interaction with other medicines:

At co-administration of the drugs possessing a strong inhibiting effect nacyp3a4 (such as antifungal means of group of azoles and makrolidny antibiotics), concentration of a kvetiapin in plasma can increase.

In such cases it is necessary to apply lower doses of a kvetiapin. The special attention has to be paid to the elderly and weakened patients. It is necessary to estimate individually a ratio of risk and advantage for each patient.

Inductors of microsomal systems of a liver (Phenytoinum, etc.), thioridazine increase clearance of a kvetiapin, inhibitors of microsomal systems of a liver — reduce; at the same time co-administration of a kvetiapin and antidepressants — Imipraminum (CYP2D6 inhibitor) or fluoxetine (CYP3A4 and CYP2D6 inhibitor) has no significant effect on its pharmacokinetics.

The pharmacokinetics of a kvetiapin significantly does not change at co-administration with antipsychotic drugs risperidony or a haloperidol.

Does not cause induction of the fermental systems of a liver involved in antipyrine metabolism.

The pharmacokinetics of drugs of lithium does not change at co-administration of a kvetiapin.

Clinically significant changes of pharmacokinetics of valproic acid and kvetiapin at joint purpose of a divalproyeks of sodium (sodium Valproatum and valproic acid in a molar ratio 1:1) and Kvetiapina are noted.

The medicines oppressing the central nervous system and ethanol increase risk of development of side effects.

Contraindications:

Hypersensitivity to any of drug components.

Safety and efficiency of a kvetiapin at children and teenagers was not investigated therefore use for this category of patients is not recommended.

With care: Arterial hypotension, epilepsy and epileptic seizures (in the anamnesis).

Use during pregnancy and breastfeeding: Safety and efficiency of a kvetiapin at pregnant women are not established.

Therefore, during pregnancy кветиапин it is possible to apply only if the expected advantage justifies potential risk.

Degree of excretion of a kvetiapin with women's milk is not known. Women need to recommend to avoid chest feeding during reception of a kvetiapin.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 25 mg, 100 mg, 200 mg and 300 mg.

On 10 or 30 tablets (a dosage of 25 mg and 100 mg) and on 10 or 15 tablets (a dosage
200 mg and 300 mg) in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 3, 6 blister strip packagings on 10 tablets or on 2, 4 blister strip packagings on 15 tablets or on 1, 2 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.