Кетилепт

General characteristics. Structure:

Active ingredient: each tablet contains 25 mg, 100 mg, 150 mg, 200 mg or 300 mg of active agent of a kvetiapin (in the form of 28,78 mg, 115,13 mg, 172,70 mg, 230,26 mg and 345,40 mg of a kvetiapin of a fumarat respectively).

Excipients: cellulose microcrystallic, lactoses monohydrate, sodium carboxymethylstarch (type A), povidone, magnesium stearate, silicon dioxide colloid, anhydrous. The cover contains: to a gipromelloz, titanium dioxide, lactoses monohydrate, macrogoal 4000, triacetin (триацетилглицерол). The cover of tablets of 150 mg and 200 mg also contains dye ferrous oxide yellow and dye ferrous oxide red.

Description: Tablets film coated 25 mg:bely or almost white, round biconvex tablets film coated, with a letter E engraving on one party and number 201 – on other party of a tablet, without or almost inodorous

Tablets film coated 100 mg:bely or almost white, round biconvex tablets film coated, with an engraving of a letter E and number 202 on one party of a tablet, without or almost inodorous

Tablets film coated 150 mg:rozovy, round biconvex tablets film coated, with an engraving of a letter E and number 203 on one party of a tablet, without or almost inodorous

Tablets film coated 200 mg:temno-pink, round biconvex tablets film coated, with an engraving of a letter E and number 204 on one party of a tablet, without or almost inodorous

Tablets film coated 300 mg:bely or almost white, round biconvex tablets film coated, with an engraving of a letter E and number 205 on one party of a tablet, without or almost inodorous

Pharmacological properties:

Pharmacodynamics. The mechanism действияКветиапин 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 also has higher affinity to histamine and to a1-adrenoceptors and smaller in relation to a2-adrenoceptors. Appreciable affinity of a kvetiapin to cholinergic muskarinovy and benzodiazepine receptors is not revealed. In standard tests кветиапин shows antipsychotic activity.

Pharmakodinamichesky effects. Results of studying of extrapyramidal symptoms (EPS) at animals revealed that кветиапин causes a weak katalepsy in the dose which is effectively blocking dopamine D2 receptors. Kvetiapin causes the selection reduction of activity mesolimbic A10 of dofaminergichesky neurons in comparison with A9 the nigrostriarny neurons involved in motor function. During clinical trials (in a dose of 75-750 mg/days) distinctions between use of a kvetiapin and placebo on the frequency of emergence of cases of extrapyramidal symptomatology and on the accompanying use of anticholinergic drugs are not revealed. Kvetiapin does not cause long increase in concentration of prolactin in a blood plasma. In numerous researches with the fixed dose distinctions in prolactin level when using a kvetiapin or placebo are not revealed. In clinical trials кветиапин showed efficiency at treatment and positive and negative symptoms of schizophrenia. Impact of a kvetiapin on receptors 5HT2 and D2 continues till 12 o'clock after administration of drug.

Pharmacokinetics. At oral administration кветиапин it is well soaked up from digestive tract and actively metabolized in a liver. The main metabolites which are in plasma have no the expressed pharmacological activity. Meal significantly does not influence bioavailability of a kvetiapin. The elimination half-life makes about 7 hours. About 83% of a kvetiapin contact proteins of plasma. The pharmacokinetics of a kvetiapin linear, distinctions of pharmacokinetic indicators at men and women is not observed. 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 plasma clearance of a kvetiapin is about 25% less at patients with a heavy renal nelostatochnost (clearance of creatinine less than 30 ml/min. / 1.73м2) and at patients with damage of a liver (the stabilized alcoholic cirrhosis), but individual indicators of clearance are in the limits corresponding to healthy people. About 73% of a kvetiapin are removed with urine and 21% with excrements. Less than 5% of a kvetiapin are not exposed to metabolism and is removed in an invariable look by kidneys or with fekaliyamiustanovleno that CYP3A4 is key enzyme of metabolism of the kvetiapin mediated by P450 cytochrome. In a research of pharmacokinetics of a kvetiapin in various dosage at purpose of a kvetiapin before reception of a ketokonazol or along with ketokonazoly, led to increase, on average, the maximum concentration (Cmax) and the area under a curve "concentration - time" for 235% and 522%, respectively, and also led (AUC) of a kvetiapin to reduction of clearance of a kvetiapin, on average, for 84%. The elimination half-life of a kvetiapin increased, but the average time of achievement of the maximum concentration (tmax) did not change. Kvetiapin and some of his metabolites have the weak inhibiting activity in relation to enzymes of P450 1A2, 2C9, 2C19, 2D6 and 3A4 cytochrome, but only at concentration, at 10-50 times, the exceeding concentration, observed at usually used effective dosage of 300-450 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 P450 cytochrome of the mediated metabolism of other medicines to clinically expressed inhibition.

Indications to use:

Acute and chronic psychoses, including schizophrenia. Treatments of maniacal episodes at bipolar disorder.

Route of administration and doses:

KETILEPT should accept inside 2 times a day, irrespective of meal. The Vzroslye:summarny daily dose in the first 4 days of therapy makes 50 mg (the 1st day), 100 mg (the 2nd day), 200 mg (the 3rd day) and 300 mg (the 4th day). Since 4th day the usual effective daily dose of drug of Ketilept makes 300 mg. Depending on clinical reaction and portability at each patient, the dose can be specified ranging from 150 mg to 750 mg a day. Safety of daily doses higher than 800 mg in clinical trials was not estimated. For treatment of acute maniacal episodes at bipolar disorder: the total daily dose in the first 4 days of therapy makes 100 mg (the 1st day), 200 mg (the 2nd day), 300 mg (the 3rd day) and 400 mg (the 4th day). Further selection of a dose to 800 mg a day by 6th day is possible with increase no more than on 200 mg a day. Depending on clinical reaction and portability at each patient, the dose can be specified ranging from 200 mg to 800 mg a day. The usual effective dose is ranging from 400 to 800 mg a day.

Elderly a patsiyenty:rekomenduyemy initial dose of 25 mg a day, and then it is necessary to increase a dose on 25 - 50 mg a day before achievement of an effective dose which is usually lower, than at young patients. Similarly, more careful selection of a dose and reduced doses are recommended for the weakened patients or predisposed to hypotensive reactions. To children and teenagers: Efficiency and safety of a kvetiapin at children and teenagers is not established. Renal and liver failure. It is recommended to begin therapy with 25 mg a day, then to daily raise a dose on 25 - 50 mg to achievement of an effective dose, depending on clinical reaction of the patient and individual portability.

Maintenance therapy: It is reasonable to apply the lowest dose to maintenance of remission. Patients should be investigated periodically for the purpose of definition of need of a maintenance therapy. Resuming of the interrupted course of treatment at the patients who were earlier receiving кветиапин: When resuming therapy less than in 1 week after drug withdrawal of Ketilept, administration of drug can be continued in the dose used for a maintenance therapy. When resuming therapy at patients who did not receive Ketilept more than 1 week it is necessary to carry out rules of initial selection of a dose and to establish an effective dose on clinical reaction of the patient.

Features of use:

Cardiovascular diseases: Кетилепт it is necessary to apply with care at patients with the diagnosed cardiovascular diseases, vascular diseases of a brain or other states contributing to hypotension. Кетилепт can cause orthostatic hypotension, especially in an initial stage of specification of a dose; it occurs at elderly more often, than at young patients. The interrelation between reception of a kvetiapin and increase in a QTc-interval is not revealed. However, at purpose of a kvetiapin along with the drugs extending QTS interval it is necessary to be careful, especially at elderly people.

Convulsive attacks. Distinctions in the frequency of development of spasms in the patients accepting Kvetiapin or placebo are not revealed. However, also as well as at therapy by other antipsychotic drugs, it is recommended to be careful at treatment of patients with existence of convulsive attacks in the anamnesis.

Late dyskinesia: Кетилепт, as well as other antipsychotic means, at prolonged use can cause late dyskinesia. In case of signs and symptoms of late dyskinesia it is necessary to consider a question of a dose decline or drug withdrawal of Ketilept.

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. In such cases Kvetiapin has to be the corresponding treatment is cancelled and is carried out.

Reactions of sudden cancellation: Symptoms of acute cancellation, including nausea, vomiting, and sleeplessness, are described seldom or never after the sharp termination of reception of high doses of antipsychotic drugs. A recurrence of symptoms of psychosis and emergence of the frustration connected with the involuntary movements (an akathisia, dystonia and dyskinesia) are possible. Therefore in case of need the terminations of administration of drug the gradual dose decline is recommended.

Lactose intolerance: By drawing up a diet for patients with a lactose intolerance it is necessary to consider that tablets film coated 25 mg, 100 mg, 150 mg, 200 mg and 300 mg contain lactoses respectively 4,42 mg, 17,05 mg, 25,47 mg, 34,1 mg and 50,94 mg. Patients should not appoint this drug with rare inherited disorders of tolerance to a galactose, hereditary deficit of lactose the Sami or a glucose galactose not absorption syndrome. In view of that кветиапин, mainly, influences the central nervous system, Kvetiapin has to be used with care in a combination with other drugs possessing the oppressing action on the central nervous system or alcohol.

Influence on ability of control of vehicles and mechanisms. Owing to influence on the central nervous system of Ketilept can cause drowsiness. Therefore at the first stages of treatment, during individually defined span, it is necessary to prohibit the patient control of mechanical vehicles or dangerous mechanisms. Further extent of restrictions should be established for each patient individually.

Side effects:

The most frequent side effects of a kvetiapin are drowsiness, dizziness, dryness in a mouth, a moderate adynamy, a lock, tachycardia, orthostatic hypotension and dyspepsia. According to summary data of clinical trials the number of the patients who stopped administration of drug because of side effect is approximately identical in the groups receiving placebo and кветиапин. As well as in case of use of other antipsychotic means, during reception of a kvetiapin faints, a malignant antipsychotic syndrome, a leukopenia, a neutropenia and peripheral hypostases are noted. The undesirable phenomena observed at introduction of a kvetiapin and classified by systems of an organism are listed below in such order: very frequent> 1/10); frequent (<1/10 and> 1/100); infrequent (<1/100 and> 1/1000); rare (<1/1000); very rare (<1/10,000). System of blood and lymph Frequent: leukopenia 3. Infrequent: eosinophilia. Very rare: neutropenia 3. Disturbances of immune system Infrequent: hypersensitivity. Metabolism and pitaniyechasty: increase in the body weight 4, increase in serumal transaminases (ALT, nuclear heating plant) 5. Very rare: hyperglycemia 1, 7, diabetes mellitus 1, 7. Dysfunctions nervous системыОчень frequent: dizziness 1, 6, drowsiness 2. Frequent: headache, alarm, psychomotor excitement, tremor, faints 1, 6. Infrequent: epileptic seizures 1. Dysfunctions are serdtsachasty: tachycardia 1, 6. Vascular narusheniyachasty: orthostatic hypotension 1, 6. Disturbances of breath and functions of bodies of a chest cavity and sredosteniyachasty: rhinitis, pharyngitis. Disturbances of functions gastrointestinal traktachasty: dryness in a mouth, a lock, diarrhea, dyspepsia, an abdominal pain. Disturbances of functions of reproductive organs and milk zhelezredky: priapism. The general disturbances and condition of fabrics in an injection site. Frequent: easy adynamy, peripheral hypostases. Rare: malignant antipsychotic syndrome 1. Laboratory issledovaniyanechasty: increase in level of gamma GT5, increase in level of triglycerides after meal, increase in the general cholesterol. Other: back pain, thorax pain, subfebrile condition, mialgiya, xeroderma, decrease in visual acuity. (1) See the section "Special Instructions and Precautionary Measures at Use". (2) Drowsiness, especially for the first two weeks of a course of treatment which usually passes at continuation of use of drug of Ketilept is possible. (3) In controlled clinical trials of a kvetiapin cases of a steady heavy neutropenia or an agranulocytosis are noted. During observation after drug registration the leukopenia and/or a neutropenia passed after the termination of introduction of a kvetiapin. Earlier existing decrease in number of white blood cells and existence of a medicinal leukopenia and/or neutropenia in the anamnesis belong to number of possible risk factors of a leukopenia and/or neutropenia. (4) Increase in body weight is preferential observed on the first weeks of treatment. (5) At some patients during introduction of a kvetiapin asymptomatic increases in serumal transaminases (ALT, nuclear heating plant are noted) or gamma GT. These increases usually took place at continuation of introduction of a kvetiapin. (6) As well as other antipsychotic means with alpha 1-adrenoceptor blocking activity, Ketilept can cause orthostatic hypotension with dizziness, tachycardia and (in some patients) faints, especially in an initial stage of selection of a dose. See the section 4.4 "Special Instructions and Precautionary Measures at Use". (7) Seldom or never during reception of a kvetiapin the hyperglycemia and deterioration in a course of earlier existing diabetes are noted. Connection of reception of a kvetiamin with the decrease in levels of hormone of a thyroid gland (T4 and free T4) caused by small doses is established. The maximum decrease occurred for the first two or four weeks of reception of a kvetiapin, but at a long course of treatment further decrease did not happen. Almost in all cases the termination of reception of a kvetiapin led to recovery of the T4 levels and free T4 irrespective of duration of a course of treatment. Less considerable decrease in T3 and reverse T3 was observed only at higher doses of a kvetiapin. the TTG and TSG levels (thyroxine - the connecting globulin) remained invariable. Clinically expressed hypothyroidism is not found. As well as other antipsychotic means, кветиапин lengthening of an interval of QTc can cause, but in clinical tests this effect was not constant. Reactions to sudden drug withdrawal are described (see. Special instructions).

Interaction with other medicines:

Phenytoinum: The combination of drug of Ketilept to Phenytoinum leads to increase in clearance of a kvetiapin in plasma since Phenytoinum induces an isoenzyme 3A4 of P450 cytochrome. The combination of a kvetiapin (on 250 mg three times a day) and Phenytoinum (on 100 mg twice a day) by 5 times increased average clearance of a kvetiapin after peroral introduction. For correction of symptoms of schizophrenia at the patients receiving at the same time кветиапин and Phenytoinum the raised doses of drug of Ketilept or other inductors of liver enzymes can be required (for example, carbamazepine, barbiturates, rifampicin or glucocorticoids). In these cases care at cancellation of Phenytoinum and/or transition to Valproatum which does not possess enzyme - the inducing properties is required. Carbamazepine: Combined use with carbamazepine considerably increased clearance of a kvetiapin that reduced system exposure of a kvetiapin. Owing to such interaction use of higher doses of drug of Ketilept can be required. P450 3A inhibitors: Combined use with ketokonazoly (on 200 mg a day within 4 days), strong inhibitor of enzyme of P450 3A cytochrome, reduced clearance of a kvetiapin after peroral introduction by 84% therefore concentration of a kvetiapin in a blood plasma increased on average by 235%. Therefore care at a combination of drug of Ketilept is necessary with ketokonazoly and other inhibitors of P450 cytochrome, azolovy antifungal drugs and makrolidny antibiotics (for example, itrakonazoly, flukonazoly and erythromycin); the corresponding dose decline of a kvetiapin is necessary. Cimetidinum: Daily regular introduction of Cimetidinum (on 400 mg three times a day within 4 days) which is nonspecific inhibitor of enzymes, led to 20% decrease in average clearance of a kvetiapin (150 mg three times a day) from plasma after peroral introduction. At simultaneous use of drug of Ketilept with Cimetidinum there is no need to change a dose of drug of Ketilept. Thioridazine: Thioridazine (on 200 mg 2 times a day) for 65% increased clearance of a kvetiapin (on 300 mg 2 times a day) from plasma after peroral introduction. Risperidon and haloperidol: The combination of a kvetiapin (on 300 mg twice a day) with antipsychotic means a haloperidol (on 7,5 mg twice a day) or рисперидон (on 3 mg twice a day) did not change equilibrium pharmacokinetics of a kvetiapin. Fluoxetine and Imipraminum: The combination of a kvetiapin (on 300 mg twice a day) with antidepressant and CYP3A4 and CYP2D6 inhibitor fluoxetine (on 60 mg once a day) or the known CYP2D6 inhibitor Imipraminum (on 75 mg twice a day) did not change equilibrium pharmacokinetics of a kvetiapin. Influence of drug of Ketilept on other medicines Antipyrine: Repeated daily introduction of a kvetiapin (to 750 mg a day at triple reception) did not cause clinically significant changes of clearance of antipyrine or its metabolites. It demonstrates to what кветиапин does not possess the essential oppressing action on the liver enzymes participating in the antipyrine metabolism mediated by P450 cytochrome. Lithium: The combination of a kvetiapin (on 250 mg three times a day) with lithium did not influence any pharmacokinetic parameters of lithium in an equilibrium state. Lorazepam: The average clearance of lorazepam after intake (a single dose of 2 mg) decreased by 20% during reception of a kvetiapin (on 250 mg 3 times a day). Smoking did not influence clearance of a kvetiapin from a blood plasma. Clinical trials showed what кветиапин exponentiates cognitive and motor effects of alcohol at patients with psychoses. Therefore it is not necessary to accept alcohol during a course of treatment drug of Ketilept.

Contraindications:

Hypersensitivity to any of drug components, children's age (efficiency and safety are not investigated). Pregnancy and period of a lactation. Category on influence on pregnancy: C. Safety and efficiency use of a kvetiapin during pregnancy is not established. Ketilpet should not be applied at pregnancy, except for cases when the advantage for mother exceeds possible risk for a fruit. Feeding period breast: It is not known whether it is allocated кветиапин in breast milk at the person. Therefore the feeding women are recommended to refuse breastfeeding during administration of drug of Ketilept. With care - at patients with the cardiovascular and cerebrovascular diseases or other states contributing to arterial hypotension, advanced age, a liver failure, convulsive attacks in the anamnesis.

Overdose:

Data on overdose of a kvetiapin are limited. Symptoms: noted symptoms generally were a consequence of strengthening of the known pharmacological effects of drug, such as drowsiness and excessive sedation, tachycardia and lowering of arterial pressure. It was extremely seldom reported about the cases of heavy overdose of a kvetiapin leading to death or a coma.

Treatment: there are no specific antidotes to a kvetiapin. In cases of serious intoxication it is necessary to consider the possibility of symptomatic therapy and it is recommended to hold the events directed to maintenance of function of breath, cardiovascular system, ensuring adequate oxygenation and ventilation. Medical observation has to be continued to an absolute recovery of the patient.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 25, 100, 150, 200, 300 mg. On 30 or 60 tablets in a bottle from brown glass with a polyethylene cover with control of the first opening and with the shock-absorber an accordion. 1 bottle together with the application instruction in a cardboard pack. Or on 10 tablets in the blister from PVH/PVDH/al.folga, on 3 or 6 blisters in a cardboard pack together with the application instruction.