Klopiksol

General characteristics. Structure:

Active ingredient: 2,364 mg, 11,82 mg or 29, 55 mg of a zuklopentiksol of dihydrochloride that there correspond 2 mg, 10 mg or 25 mg of a zuklopentiksol.

Excipients: potato starch, lactoses monohydrate, cellulose microcrystallic, кросповидон, глицерол 85%, talc, the hydrogenated castor oil, magnesium stearate.

Cover: gipromelloza, macrogoal 6000, titanium dioxide (E171), ferrous oxide red.

Pharmacological properties:

Pharmacodynamics. Klopiksol is antipsychotic drug (neuroleptic) of group of thioxanthenes. Antipsychotic action of neuroleptics is connected with blockade of dopamine receptors, and also, perhaps, blockade of 5-HT (5-gidroksitriptaminovy) receptors.

In vitro зуклопентиксол has high affinity to dopamine receptors of D1 and D2, and also α1-адренорецепторам and to serotoninovy receptors 5-HT2, but has no affinity to muskarinovy cholinergic receptors. Drug has weak affinity to H1 to histamine receptors, and has no α2-адреноблокирующей activity. In vivo affinity to D2 to receptors prevails over affinity to D1 to receptors. As the majority of neuroleptics зуклопентиксол increases prolactin level in blood serum.

Zuklopentiksol is intended for treatment of acute and chronic psychoses and for treatment of mentally retarded patients with a hyperactive and agressive behavior. In addition to considerable easing or full elimination of the main symptoms of schizophrenia such as hallucinations, nonsense and disorders of thinking, зуклопентиксол also has the expressed effect on the accompanying symptoms – hostility, suspiciousness, agitation and aggression. Zuklopentiksol renders passing, dozozavisimy sedation. Bystry development of sedation at the beginning of therapy usually is advantage at treatment of acute psychoses. Tolerance to nonspecific sedation of drug develops quickly. Specific braking
Klopiksol's action is especially favorable at treatment of patients with agitation, concern, hostility or aggression.

Pharmacokinetics. Bioavailability of a zuklopentiksol at oral administration makes about 44%. The maximum concentration in blood serum is reached approximately in 4 hours. The seeming volume of distribution (Vd) β makes about 20 l/kg. Linkng with proteins of a blood plasma about 98-99%. Zuklopentiksol slightly gets through a placental barrier and in small amounts is allocated with breast milk. The elimination half-life makes about 20 hours. Metabolites have no antipsychotic activity and are allocated, generally with a stake and, partially, with urine.

At a maintenance therapy at patients with schizophrenia with easy or moderate disease severity the level of concentration of drug in serum in 2,8-12 ng/ml (7-30 nmol/l) is recommended minimum (that is measured just before introduction).

Indications to use:

- Acute and chronic schizophrenia and other psychotic frustration, especially with hallucinations, paranoid nonsense and disturbances of thinking, and also conditions of agitation, the increased concern, hostility or aggression.
- Maniacal phase of maniac-depressive psychosis.
- Agitation and other disorders of behavior at mentally retarded patients.

Route of administration and doses:

Pill is taken inside: swallow, washing down with water. Doses of drug have to be selected individually depending on a condition of the patient. As a rule, originally it is necessary to use small doses (from 2-10 mg and above depending on the indication) which then are quickly increased to optimum depending on clinical effect. The maintenance dose can be appointed once a day before going to bed.

Bad attack of schizophrenia, other acute psychotic frustration, the expressed agitation and mania. Usually 10-50 mg/day. At the expressed frustration and conditions of moderate severity the initial dose in 20 mg/days can increase if necessary by 10-20 mg in 2-3 days to 75 mg a day or more. The maximum single dose makes 40 mg. The maximum daily dose – 150 mg.

Chronic psychotic states at schizophrenia and other chronic psychoses. Maintenance dose of 20-40 mg/days.

Agitation at mentally retarded patients. Usually 6-20 mg/days. If necessary the dose can increase to 25-40 mg/days.

Elderly patients: elderly patients need to appoint the minimum doses from the possible range of doses (2-6 mg and above).

Reduced function of a liver: клопиксол it is necessary to apply with care at patients with a liver failure. Patients with the broken function of a liver should appoint a half of the recommended doses, and also whenever possible to carry out monitoring of level of drug in blood serum.

Reduced function of kidneys: клопиксол it can be appointed in usual doses to patients with reduced function of kidneys.

Features of use:

At long therapy, especially high doses (it is higher than 25-40 mg/days), it is necessary to carry out careful control, periodically estimating a condition of patients to make the decision on a possibility of reduction of a maintenance dose.

At therapy the possibility of development of the malignant antipsychotic syndrome (MAS) exists any neuroleptics. The main symptoms of ZNS are the hyperthermia, muscular rigidity and disturbance of consciousness in combination with dysfunction of the autonomic nervous system (labile arterial pressure, tachycardia, the increased sweating). Except the immediate termination of reception of neuroleptics use of the general supporting measures and a symptomatic treatment is extremely necessary.

At the accompanying diabetes mellitus Klopiksol's appointment can change the content of insulin and glucose in blood that can demand dose adjustment of hypoglycemic drugs.

As well as other drugs belonging to a therapeutic class of neuroleptics, Klopiksol can cause lengthening of an interval of QT.

Constantly extended intervals of QT can increase risk of developing of malignant arrhythmias. It was reported about cases of development of a venous thromboembolism against the background of reception of neuroleptics. Because the patients who are on treatment by neuroleptics often enter into risk group of development of a venous thromboembolism, prior to the beginning of and during treatment by Klopiksol it is necessary to define risk factors of development of a venous thromboembolism and to take precautionary measures.

During randomized placebos - controlled clinical trials of use of some atypical antipsychotic drugs for patients with dementia 3-fold increase in risk of emergence of cerebrovascular side reactions was observed. The mechanism of such increase in risk is unknown. It is impossible to exclude increases in risk and at use of other antipsychotic means for other groups of patients. At patients with risk of development of a stroke it is necessary to apply Klopiksol with care.

Data of two big observation researches showed that at the elderly patients with dementia accepting antipsychotic drugs slight increase of risk of death, in comparison with the patients who were not accepting neuroleptics was noted. There are no sufficient data for exact assessment of size of risk and the reasons of its increase.

Klopiksol is not registered for treatment of behavioural frustration at elderly patients with dementia. At alcohol intake against the background of treatment zuklopentiksoly strengthening of the oppressing action on TsNS is possible.

Tablets contain the hydrogenated castor oil that can cause a gastric disturbance and diarrhea.

Use at pregnancy and during breastfeeding: during pregnancy Klopiksol it is necessary to apply, only if the estimated advantage for mother exceeds potential risk for a fruit.

At newborns whose mothers accepted neuroleptics at the end of pregnancy or at the time of delivery, symptoms of intoxication, such as lethargy, tremor and hyperexcitability can be observed. Besides, at such newborns the low point on a scale Apgar is noted.

During treatment by Klopiksol feeding is allowed by a breast if it is recognized as clinically necessary. Nevertheless, it is recommended to watch a condition of the newborn, especially in the first 4 weeks after the birth.

Influence on ability to manage vehicles, mechanisms: patients have to be warned about sedative effect of drug and about possible influence of its reception on ability of driving of motor transport and control of mechanisms.

Side effects:

The majority of side effects are dozozavisimy. Frequency of emergence of side effects and their intensity are most expressed at early stages of treatment and decrease in process of therapy continuation. Information on the frequency of emergence of side effects is provided on the basis of the given literature and spontaneous messages. Frequency is specified as: very often (≥1/10), it is frequent (from ≥1/100 to <1/10), infrequently (from ≥1/1000 to <1/100), is rare (from ≥1/10000 to <1/1000), is very rare (<1/10000), or it is unknown (it is impossible to estimate on the basis of the existing data).

From a nervous system: very often – drowsiness, an akathisia, a hyperkinesia, a hypokinesia; often - a tremor, dystonia, a muscle hyper tone, dizziness, a headache, paresthesias, disturbances of attention, amnesia, gait disturbances; infrequently – late dyskinesia, a hyperreflexia, parkinsonism, a syncope, alalias, dyskinesia, an ataxy, a hypotone, convulsive frustration, migraine; very seldom – a malignant antipsychotic syndrome.

From mental activity: often - sleeplessness, a depression, alarm, nervousness, agitation, unusual dreams, decrease in a libido; infrequently – apathy, increase a libido, dreadful dreams, confusion of consciousness.

From cardiovascular system: often - tachycardia, a heart consciousness; infrequently - a lowering of arterial pressure, "inflows"; seldom – the extended QT interval on the electrocardiogram; very seldom – a venous thromboembolism.

From organs of sight: often - accommodation disturbance, a vision disorder; infrequently - a mydriasis (mydriasis), the involuntary movement of eyeglobes.

From an acoustic organ and a labyrinth: often - dizziness; infrequently – a hyperacusia, a sonitus.

From respiratory system: often – an asthma, a nose congestion.

From the alimentary system: very often - dryness in a mouth; often - the increased salivation, a lock, vomiting, dyspepsia, diarrhea; infrequently – an abdominal pain, nausea, a meteorism.

Metabolic disturbances and frustration of food: often - increase in appetite, increase in body weight; infrequently – a loss of appetite, decrease in body weight; seldom – a hyperglycemia, disturbance of tolerance to glucose, a lipidemia.

From reproductive system: infrequently - disturbances of an ejaculation, erectile dysfunction, disturbance of an orgasm at women, vulvovaginal dryness; seldom – a galactorrhoea, a gynecomastia, an amenorrhea, a priapism.

From an urinary system: often - an urodynia, an ischuria, a polyuria.

Hepatic and gepatobiliarny disturbances: infrequently - change of laboratory indicators of function of a liver; very seldom - cholestatic hepatitis, jaundice.

From endocrine system: seldom – a giperprolaktinemiya.

From circulatory and lymphatic system: seldom - thrombocytopenia, a neutropenia, a leukopenia, an agranulocytosis.

From integuments and hypodermic cellulose: often - a hyperhidrosis, an itch; infrequently - a photosensitization, pigmentation disturbance, seborrhea, skin rash, dermatitis, a purpura.

From a musculoskeletal system: often - a mialgiya; infrequently – muscular rigidity, a lockjaw, a wryneck.

From immune system: seldom – hypersensitivity, anaphylactic reactions.

From an organism in general: often - an adynamy, fatigue, an indisposition, pains; infrequently – thirst, a hypothermia, a pyrexia.

There can be extrapyramidal frustration, especially at early stages of treatment. In most cases these side effects are successfully controlled by a dose decline and/or use of antiparkinsonichesky drugs.

However routine use of antiparkinsonichesky means for prevention of side effects is not recommended. They do not facilitate displays of late dyskinesia and can worsen them. The dose decline or if it is possible, the therapy termination zuklopentiksoly is recommended. At a persistent akathisia benzodiazepines or propranolol can be useful.

At reception of a zuklopentiksol the following side effects arising at reception and other neuroleptics were also registered: in rare instances lengthening of an interval of QT, ventricular arrhythmias – tachycardia and fibrillation, sudden death, a cardiac standstill and development of paroxysms of ventricular tachycardia (torsade des pointes).

The sharp termination of reception of a zuklopentiksol can be followed by emergence of reactions of cancellation. The most frequent symptoms - nausea, vomiting, anorexia, diarrhea, a rhinorrhea, sweating, mialgiya, paresthesias, sleeplessness, nervousness, alarm and agitation. Patients can also feel dizziness, caumesthesias and cold weather, a tremor. Symptoms, as a rule, begin within 1 - 4 days after cancellation and decrease within 7 - 14 days.

Interaction with other medicines:

Klopiksol can strengthen sedative effect of alcohol, action of barbiturates and other oppressing TsNS of substances.

Klopiksol it is not necessary to appoint together with guanetidiny and similarly operating means as neuroleptics can raise or lower effect of some anti-hypertensive means; anti-hypertensive action of a guanetidin and similarly operating drugs decreases.

Simultaneous use of neuroleptics and lithium increases risk of a neurotoxicity.

Tricyclic antidepressants and neuroleptics mutually inhibit metabolism of each other.

Klopiksol can reduce efficiency of a levodopa and effect of adrenergic drugs.

Simultaneous use with Metoclopramidum and piperazin increases risk of development of extrapyramidal disturbances.

As зуклопентиксол it is partially metabolized by CYP2D6 isoenzyme, the concomitant use with the drugs inhibiting this isoenzyme can lead to decrease in clearance of a zuklopentiksol.

The increase in an interval of QT characteristic of therapy by antipsychotic means, can be strengthened at a concomitant use of the drugs extending QT interval: antiarrhytmic IA and III medicines of classes (quinidine, Amiodaronum, соталол, дофетилид), some antipsychotic means (thioridazine), some antibiotics macroleads (erythromycin) and antibiotics of a hinolonovy row (гатифлоксацин, moxifloxacin), some antihistamines (терфенадин, астемизол), and also a tsizaprida, lithium and other medicines increasing QT interval. It is necessary to avoid a concomitant use of Klopiksol and the drugs stated above.

Klopiksol it is necessary to appoint with care along with the drugs causing electrolytic disturbances (thiazide and tiazidopodobny diuretics) and the drugs capable to increase concentration of a zuklopentiksol in a blood plasma, because of possible increase in risk of lengthening of an interval of QT and developing of life-threatening arrhythmias.

Contraindications:

- Hypersensitivity to a zuklopentiksol or any of excipients.
- The known hypersensitivity to drugs of group of thioxanthenes.
- Acute intoxication ethanol, barbiturates and opiates.
- A collapse, the oppression of consciousness of any origin, lump assumed or the established subcortical injury of a brain.
- Hereditary intolerance of a galactose, insufficiency of lactase or disturbance of absorption of glucose and galactose.

With care: organic diseases of a brain, mental retardation, convulsive frustration, a liver failure, cardiovascular diseases in the anamnesis, including lengthening of an interval of QT, bradycardia <50 beats per minute, recently postponed acute myocardial infarction, dekompensirovanny heart failure, arrhythmia, a hypopotassemia, a hypomagnesiemia and genetic predisposition to such states, existence of risk factors of development of a stroke (including acute arteriosclerosis), parkinsonism, opioid and alcohol addiction; pregnancy, breastfeeding period; children's and teenage age up to 18 years (because of insufficiency of clinical data).

Overdose:

Symptoms. Drowsiness, coma, motive frustration, spasms, shock, hyperthermia/hypothermia. At overdose along with administration of drugs, exerting impact on cordial activity, changes on an ECG, lengthening of an interval of QT, polymorphic piruetny ventricular tachycardia, a cardiac standstill and ventricular arrhythmias were registered.

Treatment. Symptomatic and supporting. The measures directed to maintenance of activity of respiratory and cardiovascular systems have to be taken. It is not necessary to use Epinephrinum (adrenaline) since it can lead to the subsequent lowering of arterial pressure. Spasms can be stopped diazepam, and motive frustration by Biperidinum.

Storage conditions:

Klopiksol's tablets have to be stored at a temperature not above 25 °C. On each packaging expiry date of the validity is specified. To store in places, inaccessible to children. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated on 2 mg, 10 mg, 25 mg. Each tablet contains a zuklopentiksol dihydrochloride in the number corresponding of 2 mg, 10 mg or 25 mg of a zuklopentiksol. Packagings: 2 mg on 50 and 100 tablets; 10 mg on 50 and 100 tablets; 25 mg on 50 and 100 tablets.