Квентиакс®

General characteristics. Structure:

Active ingredient: 28,78 mg, 115,13 mg, 172,69 mg, 230,26 mg, 345,39 mg of a kvetiapin of a gemifumarat (a kvetiapin of a fumarat) that there correspond 25 mg, 100 mg, 150 mg, 200 mg and 300 mg of a kvetiapin.

Excipients: lactoses monohydrate,  calcium  hydrophosphate dihydrate, cellulose microcrystallic,  povidone,    sodium carboxymethylstarch    (type A), magnesium stearate.

The cover is film: gipromelloza, titanium E171 dioxide, macrogoal-4000.

Cover of tablets in 25 mg:krasitel ferrous oxide yellow, E172, dye ferrous oxide red, E172.N05.

Antipsychotic psychotropic drug.

Pharmacological properties:

Pharmacodynamics. Kvetiapin is atypical antipsychotic drug which shows higher affinity to receptors of serotonin (5HT2), than to receptors of D1 and D2 dopamine of a brain. Kvetiapin has affinity to histamine and alfa-1 to receptors, and smaller affinity  in relation to alfa-2 to receptors. Appreciable affinity   of a kvetiapin   to   cholinergic   muskarinovy   and   benzodiazepine receptors is not revealed. In standard tests кветиапин shows antipsychotic activity. Pharmakodinamichesky effects revealed Results of studying of extrapyramidal symptoms (EPS) at animals that кветиапин causes a weak katalepsy in the dose which is effectively blocking dopamine D2    receptors. 

Kvetiapin    causes    the selection    reduction    of activity of mesolimbic Ai-dofaminergichesky neurons, in comparison with A9-nigrostriatnymi the neurons involved in motive functions. Clinical performance distinctions between use of a kvetiapin (in a dose of 75-750 mg/days) and placebo on   the frequency   of emergence of cases   of extrapyramidal   symptomatology   and   on the accompanying use   of anticholinergic  drugs are not revealed.      Does not cause long increase in concentration of prolactin in a blood plasma. Kvetiapin it is long supports clinical improvement at those patients at whom the positive effect developed in the initiation of treatment. Duration of impact of a kvetiapin on receptors 5HT2 - serotoninovy and D2 - dopamine receptors makes less than 12 hours after administration of drug.

Pharmacokinetics. Absorption - high, meal does not influence bioavailability. Communication with proteins of plasma - 83%. The pharmacokinetics of a kvetiapin has linear character and does not differ at men and women. It is actively metabolized in a liver with formation pharmacological of inactive metabolites    under the influence of    CYP3A4 enzyme    of P450 cytochrome. 

Kvetiapin  and some of his metabolites are weak inhibitors of isoenzymes 1A2, 2S9, 2S19, 2D6 and ZA4 of P450 cytochrome of the person, but only in concentration, at least, at 10-50  times  exceeding  concentration  of drug  at  use  in  the range of effective doses from 300 to 450 mg/days. Based on results of in vitro, it is not necessary to expect that  co-administration of a kvetiapin with other drugs will lead to clinically expressed inhibition of P450 cytochrome of the mediated metabolism of other medicines. The elimination half-life (T1/2) makes about 7 hours. It is removed by kidneys  about 73% and through intestines - 21%. Less than 5% of a kvetiapin are not exposed to metabolism and is removed in an invariable look. The average clearance of a kvetiapin at elderly patients is 30-50% less, than at patients aged from 18 up to 65 years. The average clearance of a kvetiapin of plasma at patients with a heavy renal failure (clearance of creatinine <30 ml/min. / 1,73 m3) is reduced approximately by 25% and at patients with damage of a liver (the stabilized alcoholic cirrhosis).

Indications to use:

• Treatment of acute and chronic psychoses, including schizophrenia;
• Treatment of maniacal episodes at bipolar disorder.

Route of administration and doses:

Inside, 2 times a day irrespective of meal.
Treatment of acute and chronic psychoses, including schizophrenia. The daily dose in the first 4 days makes: the 1st day - on 50 mg; the 2nd day - 200 mg; the 3rd day of-200 mg and the 4th day - 300 mg. Since fourth day, the daily dose is recommended: 300 mg. Depending on clinical effect and portability of drug its dose can individually vary from 150 mg/days to 750 mg/days. The maximum daily dose at treatment of schizophrenia - 750 mg.

Treatment of maniacal episodes at bipolar disorder: Kvetiapin is recommended as monotherapy or as adjuvant therapy for stabilization of mood.

The daily dose in the first 4 days makes: the 1st day - on 100 mg; 2nd day of 200 mg; the 3rd day of-300 mg and the 4th day - 400 mg. Increase in a daily dose is possible further on 200 mg a day and by 6th day of therapy makes 800 mg. Depending on clinical effect and portability of drug its dose can individually vary from 200 mg/days to 800 mg/days. As a rule, the effective dose makes from 400 to 800 mg/days. The maximum daily dose according to this indication - 800 mg.

Advanced age: Since the plasma clearance of a kvetiapin at elderly people is reduced by 30-50%, it is necessary to appoint drug with care, especially at the beginning of therapy. A starting dose - 25 mg/days, with the subsequent increase by 25-50 mg before achievement of an effective dose.

Renal and liver failure: At patients with a renal and liver failure it is recommended to begin therapies with 25 mg/days. Further it is recommended to increase a dose daily by 25-50 mg before achievement of an effective dose.

Features of use:

With care: patients with the cardiovascular and cerebrovascular diseases or other states contributing to arterial hypotension, inborn increase in an interval of QT on the electrocardiogram (ECG) or in the presence of the conditions potentially capable to cause increase in an interval of QT (co-administration of drugs, extending QT interval, congestive heart failure, a hypopotassemia, a gipomagneziyemiya), advanced age, a liver failure, epilepsy, convulsive attacks in the anamnesis, pregnancy.

At sharp cancellation of high doses of antipsychotic drugs the following acute reactions ("withdrawal") - 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.

At purpose of a kvetiapin along with the drugs extending QT interval it is necessary to be careful, especially at elderly people. At congestive heart failure, at a hypopotassemia and a gipomagneziyemiya. Considering what кветиапин influences the central nervous system, drug has to be used with care in a combination with other drugs possessing the oppressing action on the central nervous system. It is recommended to abstain from alcohol intake. At emergence of symptoms of late dyskinesia it is necessary to reduce a dose or to stop use of a kvetiapin.

Convulsive attacks. In controlled clinical trials also placebo was not established distinctions about the frequency of developing of spasms between kvetiapiny. However, as well as at therapy other antipsychotic means recommend to careful at treatment of patients with existence of convulsive attacks in the anamnesis. Malignant antipsychotic syndrome. The malignant  antipsychotic  syndrome  can    be connected  with  the carried-out antipsychotic treatment.

Clinical manifestations of a syndrome include: a hyperthermia, the changed mental status, muscular rigidity, instability of the autonomic nervous system, increase in level of a kreatinfosfokinaza. At development of this syndrome кветиапин has to be the corresponding treatment is cancelled and is carried out.

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 milk of mother is not established. Women need to recommend to avoid chest feeding during reception of a kvetiapin.

During treatment kvetiapiny it is recommended 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 bodies of a hemopoiesis and lymphatic system: often - a leukopenia; infrequently - an eosinophilia; very seldom - a neutropenia.

Disturbances of metabolism and food: often - the povppeniye of body weight is preferential in the first weeks of treatment); very seldom - a hyperglycemia or a decompensation of a diabetes mellitus.

  From  the central  and  peripheral  nervous  system:          dizziness, drowsiness, a headache is very frequent; often - syncopal states; infrequently - uneasiness,   excitement,   sleeplessness,   an akathisia,  a tremor,  spasms,  a depression, paresthesias; very seldom: late dyskinesia.

 From  cardiovascular  system:  often  -    tachycardia,  orthostatic arterial hypotension, lengthening of an interval of QT on an ECG.

From a respiratory organs: rhinitis, pharyngitis.

From digestive tract: often - dryness in a mouth, a lock, diarrhea, dyspepsia; seldom - jaundice, nausea, vomiting, an abdominal pain; very seldom - hepatitis.

Allergic reactions: infrequently - skin rash, hypersensitivity reactions; very seldom - a Quincke's disease, Stephens-Johnson's syndrome.

From reproductive system and mammary glands: seldom - a priapism (a painful erection).

Others: often - peripheral hypostases, an adynamy; seldom - a back pain, thorax pain, subfebrile condition, a mialgiya, a xeroderma, sight easing, a neyrolepticheskiyzlokachestvenny syndrome (a hyperthermia, consciousness disturbance, muscular rigidity, вегето - vascular disorders, increase in concentration of a kreatinfosfokinaza).

Laboratory indicators: often - a povppeniye of level of serumal transaminases (ACT or ALT); infrequently - a povppeniye of the GGT serumal level and content of triglycerides (not on an empty stomach), a hypercholesterolemia; decrease in level of hormones of a thyroid gland: the general T4 and free T4 (in the first 4 weeks), and also - the general TZ and reverse TZ (only at reception of high doses of a kvetiapin).

Interaction with other medicines:

Kvetiapin does not cause induction of the fermental systems of a liver involved in metabolism of phenazone and lithium.

Co-administration of a kvetiapin with the drugs which are potentially inhibiting liver enzymes, such as carbamazepine or Phenytoinum, and also with barbiturates, rifampicin is possible decrease in plasma concentration of a kvetiapin that can demand increase in a dose of Kventiaks, depending on clinical effect.

It needs also to be considered at cancellation of Phenytoinum or carbamazepine, or other inductor of fermental system of a liver or replacement by the drug which is not inducing microsomal enzymes of a liver (for example, a valproyevayakislota). The main enzyme which is responsible for metabolism of a kvetiapin with P450 cytochrome is CYP3A4.

The pharmacokinetics of a kvetiapin does not change at simultaneous use as Cimetidinum (P450 inhibitor) or fluoxetine (CYP3A4 and CYP2D6 inhibitor), Imipraminum antidepressant (CYP2D6 inhibitor).

It is recommended to be careful at simultaneous use of a kvetiapin and system use of CYP3A4 inhibitors { antifungal means of group of an azolova  makrolidny  antibiotics)  since  plasma  concentration  of a kvetiapin  can increase.  Therefore it is necessary to apply   lower doses of a kvetiapin.  

Special attention has to be paid to the elderly and weakened patients.

The pharmacokinetics of a kvetiapin significantly did not change at simultaneous introduction with antipsychotic   means   -  risperidony   or   galoperidony.   However, the concomitant use of a kvetiapin with thioridazine led to increase in clearance of a kvetiapin. The medicines oppressing the central nervous system (CNS) also etanolpovyshat risk of development of side effects.

Contraindications:

• Hypersensitivity to a kvetiapin or other components of drug;
• Breastfeeding period;
• Children and teenagers up to 18 years (efficiency and safety are not established).

Overdose:

Data on overdose of a kvetiapin are limited. Cases of reception of a kvetiapin in the dose exceeding 30 g are described. At most of patients side effects were not noted, side effects passed in cases of their development independently. The case of a lethal outcome at reception of 13,6 grams of a kvetiapin is registered. It was extremely seldom reported about overdose cases kvetiapiny, QT leading to lengthening of an interval, a coma or death. At patients with a serious cardiovascular illness in the anamnesis the risk of development of side effects at overdose can increase.

Symptoms: excessive sedapiya, drowsiness, tachycardia, lowering of arterial pressure.

Treatment: symptomatic; the actions directed to maintenance of function of breath, cardiovascular system, adequate oxygenation and ventilation of the lungs. There are no specific antidotes.

Storage conditions:

To store at a temperature no more than 25 °C. To store in    the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated on 25 mg, 100 mg, 150 mg, 200 mg and 300 mg. On 10 tablets in the blister (blister strip packaging). 3, 6 or 9 blisters (blister strip packagings) together with the application instruction in a pack cardboard.