Paksil

General characteristics. Structure:

Tablets, film coated white color, oval, biconvex, with an engraving "20" on one party and risky - on another.

Active ingredient: a paroksetina of a hydrochloride гемигидрат 22.8 mg that corresponds to the maintenance of a paroksetin of 20 mg

Excipients: hydrophosphate calcium a dihydrate - 317.75 mg, sodium carboxymethylstarch type A - 5.95 mg, magnesium stearate - 3.5 mg.

Structure of a cover: опадрай white - 7 mg (a gipromelloza - 4.2 mg, titanium dioxide - 2.2 mg, a macrogoal of 400 - 0.6 mg, polysorbate of 80 - 0.1 mg).

Pharmacological properties:

Paroksetin is a powerful and selection inhibitor of the return capture of a 5-gidroksitriptamin (5-HT, serotonin). It is considered to be that its antidepressive activity and efficiency at treatment of obsessivno-compulsive (ROC) and panic frustration is caused by specific oppression of the return serotonin reuptake in brain neurons.

On the chemical structure пароксетин differs from tricyclic, tetracyclic and other known antidepressants.

Paroksetin has weak affinity to muskarinovy holino-receptors, and researches on animals showed that it has only weak anticholinergic properties.

According to selective effect of a paroksetin, the research in vitro showed that it, unlike tricyclic antidepressants, has weak affinity to α1-, α2-and to β-adrenoceptors, and also to dopamine (D2), 5-HT1-like, 5NT2-and to histamine (H1) receptors. This lack of interaction with postsynaptic receptors of in vitro is confirmed by results of the researches in vivo which showed absence at a paroksetin of ability to oppress TsNS and to cause arterial hypotension.

Pharmakodinamichesky effects

Paroksetin does not break psychomotor functions and does not strengthen the oppressing effect of ethanol on TsNS.

As well as other selective serotonin reuptake inhibitors, пароксетин causes symptoms of excessive stimulation of 5-NT-retseptorov at introduction to animals who received MAO inhibitors or tryptophane earlier. Researches of behavior and changes of EEG showed what пароксетин causes the weak activating effects in the doses exceeding those which are required for inhibition of the return serotonin reuptake. By the nature its activating properties are not "amfetaminopodobny".

Researches on animals showed what пароксетин does not influence cardiovascular system.

пароксетин does not cause clinically significant changes of the ABP, ChSS and an ECG in healthy faces.

Researches showed what, unlike antidepressants which oppress the return capture of noradrenaline пароксетин has much smaller ability to inhibit anti-hypertensive effects of a guanetidin.

 

Pharmacokinetics. Absorption

After intake пароксетин well is absorbed and exposed to metabolism at "the first passing".

Owing to metabolism at "the first passing", the smaller quantity of a paroksetin comes to a system blood stream, than that which is absorbed from a GIT. In process of increase in quantity of a paroksetin in an organism at a single dose of high doses or at multiple dose of usual doses there is a partial saturation of a metabolic way of the first passing and the clearance of a paroksetin from plasma decreases. It leads to disproportionate increase in concentration of a paroksetin in plasma. Therefore its pharmacokinetic parameters are not stable, the nonlinear kinetics is a consequence of what. It should be noted, however, that nonlinearity is usually expressed poorly and it is observed only at those patients at whom against the background of reception of low doses of drug in plasma low levels of a paroksetin are reached. Stable concentration in plasma are reached in 7-14 days after an initiation of treatment paroksetiny. Its pharmacokinetic parameters, most likely, do not change during long therapy.

Distribution

Paroksetin is widely distributed in fabrics, and pharmacokinetic calculations show what in plasma remains only to 1% of all quantity of the paroksetin which is present at an organism. In therapeutic concentration about 95% of the paroksetin which is in plasma it is connected with proteins.

Correlation between concentration of a paroksetin in plasma and its clinical effect is not revealed (i.e. with side reactions and efficiency). It is established what пароксетин in small amounts gets into breast milk of women, and also into embryos and fruits of laboratory animals.

Metabolism

The main metabolites of a paroksetin are the polar and conjugated products of oxidation and methylation which eliminirutsya easily from an organism. Considering relative absence at these metabolites of pharmacological activity, it is possible to claim that they do not influence therapeutic effects of a paroksetin.

Metabolism does not worsen ability of a paroksetin to selectively inhibit the return serotonin reuptake.

Removal

With urine in the form of not changed paroksetin less than 2% of the accepted dose whereas excretion of metabolites reaches 64% of a dose are excreted. About 36% of a dose are excreted with a stake, possibly getting to it with bile; excretion with a stake of not changed paroksetin makes less than 1% of a dose. Thus, пароксетин it eliminirutsya almost entirely by means of metabolism.

Excretion of metabolites has two-phase character: in the beginning is result of metabolism of "the first passing", then it is controlled by system elimination of a paroksetin.

T1/2 of a paroksetin varies, but usually makes about 1 days (16-24 h).

Indications to use:

Depression

Depression of all types, including a situational and heavy depression, and also the depression which is followed by alarm.

At treatment of depressive frustration пароксетин has approximately the same efficiency, as well as tricyclic antidepressants. There are data on what пароксетин can yield good results at patients at whom standard antidepressants it was therapies inefficient.

Reception of a paroksetin does not exert adverse impact on quality and duration of a dream in the mornings. Besides, in process of manifestation of effect of treatment paroksetiny the dream can improve.

When using hypnagogues of short action in a combination with antidepressants additional side effects did not arise. In the first several weeks of therapy пароксетин effectively reduces symptoms of a depression and suicide thoughts.

Results of researches in which patients accepted пароксетин on an extent till 1 year showed that drug effectively prevents a depression recurrence.

Obsessivno-kompulsivnoye frustration

Paroksetin is effective at treatment of the obsessivno-compulsive frustration (OCF), including and as means of the supporting and preventive therapy. Besides, пароксетин effectively prevented a recurrence SURROUNDING.

Panic frustration

Paroksetin is effective at treatment of panic frustration with an agoraphobia and without it, including as means of the supporting and preventive therapy. It is established that at treatment of panic frustration a combination of a paroksetin and cognitive and behavioural therapy it is significant more effectively, than the isolated use of cognitive and behavioural therapy.

Besides, пароксетин effectively prevented a recurrence of panic frustration.

Social phobia

Paroksetin is an effective remedy of treatment of a social phobia, including and as the long supporting and preventive therapy.

Generalized alarming frustration

Paroksetin is effective at generalized alarming frustration, including and as the long supporting and preventive therapy. Paroksetin also effectively prevents a recurrence at this frustration.

Posttraumatic stressful frustration

Paroksetin is effective at treatment of posttraumatic stressful frustration.

Route of administration and doses:

Paroksetin is recommended to accept 1 time / morning during food. It is necessary to swallow of a tablet entirely, without chewing.

Depression

The recommended dose at adults makes 20 mg / In need of dependence on therapeutic effect the daily dose can increase weekly by 10 mg / to the maximum dose of 50 mg / As well as at treatment by any antidepressants, it is necessary to estimate efficiency of therapy and if necessary to adjust a dose of a paroksetin 2-3 weeks later after an initiation of treatment and further depending on clinical indications.

For stopping of depressive symptoms and prevention of a recurrence it is necessary to observe the adequate duration of the stopping and maintenance therapy. This period can make several months.

Obsessivno-kompulsivnoye frustration

The recommended dose makes 40 mg / Treatment begin with a dose 20 mg / which can be raised weekly on 10 mg / If necessary the dose can be raised to 60 mg / It is necessary to observe the adequate duration of therapy (several months and longer).

Panic frustration

The recommended dose is equal to 40 mg / Treatment of patients it is necessary to begin with a dose 10 mg weekly to raise a dose on 10 mg/, being guided by clinical effect. If necessary the dose can be increased to 60 mg / the Low initial dose is recommended for minimization of possible strengthening of symptomatology of panic frustration which can arise in an initiation of treatment any antidepressants. It is necessary to observe adequate terms of therapy (several months and longer).

Social phobia

The recommended dose makes 20 mg / If necessary the dose can be increased weekly by 10 mg / depending on clinical effect to 50 mg /

Generalized alarming frustration

The recommended dose makes 20 mg / If necessary the dose can be increased weekly by 10 mg / depending on clinical effect to 50 mg /

Posttraumatic stressful frustration

The recommended dose makes 20 mg / If necessary the dose can be increased weekly by 10 mg / depending on clinical effect to 50 mg /

Cancellation of a paroksetin

As well as at treatment by other psychotropic drugs, it is necessary to avoid sharp cancellation of a paroksetin.

The following scheme of cancellation can be recommended: decrease in a daily dose by 10 mg a week; after achievement of a dose of 20 mg / patients continue to accept this dose within 1 week, and only after it cancel drug completely. If symptoms of cancellation develop in time of a dose decline or after drug withdrawal, it is reasonable to resume reception of earlier appointed dose. In the subsequent the doctor can continue a dose decline, but slower.

Separate groups of patients

At elderly patients of concentration of a paroksetin in plasma can be raised, however the range of its concentration in plasma matches those at younger patients. At this category of patients therapy should be begun with the dose recommended for adults which can be raised to 40 mg /

Concentration of a paroksetin in plasma are increased at patients with a heavy renal failure (KK less than 30 ml/min.) and at patients with the broken function of a liver. Such patients should appoint the drug doses which are in the lower part of range of therapeutic doses.

Use of a paroksetin for children and teenagers (18 years are younger) contraindicated.

Features of use:

Children and teenagers (18 years are younger)

Treatment by antidepressants of the children and teenagers suffering from big depressive frustration and other mental diseases is associated with the increased risk of emergence of suicide thoughts and suicide behavior. In clinical trials the undesirable phenomena connected with suicide attempts and suicide thoughts, hostility (preferential aggression, deviant behavior and irascibility), were more often observed at the children and teenagers receiving пароксетин than at patients of this age group who received placebo. Now there are no data on long-term safety of a paroksetin for children and teenagers who would concern influence of this drug on growth, maturing, cognitive and behavioral development.

Clinical deterioration and suicide risk at adults

The young patients who are especially suffering from big depressive frustration can be subject to the increased risk of emergence of suicide behavior during therapy paroksetiny. The analysis of the researches conducted by placebo-kontroliruyemgkh at the adults having mental diseases confirms increase in frequency of suicide behavior at young patients (at the age of 18-24 years) against the background of reception of a paroksetin in comparison with group of placebo (2.19% to 0.92% respectively) though this difference is not considered statistically significant. At patients of the senior age groups (from 25 to 64 years are also more senior than 65 years) increases in frequency of suicide behavior on it was observed. At the adult all age groups suffering from big depressive frustration statistically significant increase in cases of suicide behavior against the background of treatment placebo, paroksetiny in comparison with group was observed (occurrence of suicide attempts: 0.32% to 0.05% respectively). However the majority of these cases against the background of reception of a paroksetin (8 of 11) was registered at young patients aged from 18-30 years. The data received in a research at patients with big depressive frustration can confirm increase in frequency of cases of suicide behavior at patients 24 years having various mental disorders are younger. Patients with a depression have an aggravation of symptoms of this frustration and/or emergence of suicide thoughts and suicide behavior (suitsidalnost) can be observed irrespective of whether they receive antidepressants. This risk remains until the expressed remission is reached. Improvement of a condition of the patient can be absent in the first weeks of treatment and more and therefore it is necessary to watch the patient attentively for early detection of a clinical aggravation and a suitsidalnost, especially at the beginning of a course of treatment, and also during the periods of change of doses, whether it be their increase or reduction. Clinical experience of use of all antidepressants shows that the risk of a suicide can increase at early stages of recovery.

Other mental disorders for which treatment use пароксетин can be connected with the increased risk of suicide behavior too. Besides, these frustration can represent the komorbidny states accompanying big depressive frustration. Therefore at treatment of the patients suffering from other mental disturbances it is necessary to observe the same precautionary measures, as at treatment of big depressive frustration.

The patients having in the anamnesis suicide behavior or suicide thoughts, patients of young age and also patients with the expressed suicide thoughts prior to treatment and therefore all of them need to pay special attention during treatment are exposed to the greatest risk of suicide thoughts or suicide attempts. Patients (and those who look after them) need to be warned about need to monitor deterioration in their state and/or emergence of suicide thoughts / suicide behavior or thoughts of causing to itself harm during all course of treatment, especially in an initiation of treatment, during change of a dose of drug (increase and decrease). In case of these symptoms it is necessary to ask for medical care immediately.

It is necessary to remember that such symptoms as agitation, the akathisia or a mania can be connected with a basic disease or be an effect of the applied therapy. At emergence of symptoms of clinical deterioration (including new symptoms) and/or suicide thoughts / behavior, especially at their sudden emergence, increase of weight of manifestations or if they were not a part of the previous symptom complex at this patient, it is necessary to reconsider the therapy mode up to drug withdrawal.

Akathisia

Occasionally treatment paroksetiny or other drug of the SIOZS group is followed by developing of an akathisia which is shown by feeling of internal concern and psychomotor excitement when the patient cannot quietly sit or stand; at an akathisia the patient usually feels subjective discomfort. The probability of developing of an akathisia is highest in the first several weeks of treatment.

Serotoninovy syndrome / malignant antipsychotic syndrome

In rare instances against the background of treatment paroksetiny there can be a serotoninovy syndrome or symptomatology similar to a malignant antipsychotic syndrome, especially if пароксетин use in a combination with other serotonergic drugs and/or neuroleptics. These syndromes pose a potential threat of life and therefore treatment paroksetiny needs to be stopped, in case of their emergence (they are characterized by groups of such symptoms, as a hyperthermia, muscular rigidity, a myoclonus, vegetative frustration with possible fast changings of indicators of the vital functions, the changes of the mental status including confusion of consciousness, irritability, extremely heavy agitation progressing to a delirium and a coma), and to begin the supporting symptomatic therapy. Paroksetin should not be appointed in a combination with predecessors of serotonin (such as L-tryptophane, oxytriptane) in connection with risk of development of a serotoninovy syndrome.

Mania and bipolar disorder

The big depressive episode can be initial display of bipolar disorder. It is considered to be (though it and is not proved by controlled clinical tests) that treatment of such episode only one antidepressant can increase probability of the accelerated development of the mixed / maniacal episode in the patients subject to risk of developing of bipolar disorder. Before an initiation of treatment antidepressant it is necessary to carry out careful screening for assessment of risk of emergence at this patient of bipolar disorder; such screening has to include collecting the detailed psychiatric anamnesis, including data on existence in a family of cases of a suicide, bipolar disorder and depression. Paroksetin is not registered for treatment of a depressive episode within bipolar disorder. Paroksetin it is necessary to apply with care at the patients having a mania in the anamnesis.

MAO inhibitors

Treatment paroksetiny should be begun carefully not earlier than in 2 weeks after the therapy termination with MAO inhibitors; the dose of a paroksetin needs to be raised gradually to achievement of optimum therapeutic effect.

Renal failure or liver

It is recommended to be careful at treatment paroksetiny patients with a heavy renal failure and patients with abnormal liver functions.

Epilepsy

As well as other antidepressants, пароксетин it is necessary to apply with care at patients with epilepsy.

Convulsive attacks

Frequency of convulsive attacks at the patients accepting пароксетин makes less than 0.1%. In case of developing of a convulsive attack treatment paroksetiny needs to be stopped.

Electroconvulsive therapy

There is only a limited experience of simultaneous use of a paroksetin and electroconvulsive therapy.

Glaucoma

As well as other drugs of the SIOZS group, пароксетин the mydriasis causes, and it needs to be applied with care at patients with closed-angle glaucoma.

Hyponatremia

At treatment paroksetiny the hyponatremia arises seldom and preferential at elderly patients and is leveled after cancellation of a paroksetin.

Bleedings

It was reported about hemorrhages in skin and mucous membranes (including gastrointestinal bleedings) at patients against the background of reception of a paroksetin. Therefore пароксетин it is necessary to apply with care at patients who at the same time receive the drugs increasing risk of bleedings at patients with the known tendency to bleedings and at patients with the diseases contributing to bleedings.

Heart diseases

At treatment of patients with heart diseases it is necessary to observe usual precautionary measures.

Symptoms which can arise at the treatment termination paroksetiny at adults

As a result of clinical trials at adults occurrence of the undesirable phenomena at cancellation of a paroksetin made 30% whereas occurrence of the undesirable phenomena in group of placebo made 20%.

Such symptoms of cancellation as dizziness, touch disturbances (including paresthesias, feeling of blow by electric current and a sonitus), sleep disorders (including bright dreams), agitation or alarm, nausea, a tremor, confusion of consciousness, perspiration, headaches and diarrhea are described. Usually these symptoms are expressed poorly or moderately, but some patients can have them heavy. Usually they arise in the first few days after drug withdrawal, however in rare instances arise at patients who accidentally missed reception of only one dose. As a rule, these symptoms pass spontaneously and disappear within 2 weeks, but at some patients they can last much longer (2-3 months and more). It is recommended to reduce a dose of a paroksetin gradually, for several weeks or months before its full cancellation, depending on needs of the specific patient.

Emergence of symptoms of cancellation does not mean that drug is a subject of abuse or causes dependence as it takes place in a case with drugs and psychotropic substances.

Symptoms which can arise at the treatment termination paroksetiny at children and teenagers

As a result of clinical trials at children and teenagers occurrence of the undesirable phenomena at cancellation of a paroksetin made 32% whereas occurrence of the undesirable phenomena in group of placebo made 24%.

Symptoms of cancellation of a paroksetin (emotional lability, including suicide thoughts, suicide attempts, changes of mood and tearfulness, and also nervousness, dizziness, nausea and abdominal pain) were registered at 2% of patients against the background of a dose decline of a paroksetin or after its full cancellation and met twice more often than in group of placebo.

Fractures of bones

By results of epidemiological researches of risk of fractures of bones communication of fractures of bones with reception of antidepressants, including the SIOZS group is revealed. The risk was observed during a course of treatment by antidepressants and was maximum at the beginning of a therapy course. The possibility of fractures of bones has to be considered at purpose of a paroksetin.

Tamoxifenum

Some researches showed that the efficiency of Tamoxifenum measured as the relation cancer recurrence a breast/lethality decreases at joint appointment with paroksetiny, as a result of irreversible inhibition of CYP2D6. The risk can increase at joint appointment during long time. At treatment or prevention of breast cancer it is necessary to consider the possibility of use of alternative antidepressants which do not influence CYP2D6 or influence to a lesser extent.

Influence on ability to driving of motor transport and to control of mechanisms

Clinical experience of use of a paroksetin demonstrates that it does not worsen cognitive and psychomotor functions. At the same time, as well as at treatment by any other psychotropic drugs, patients have to be especially careful during the driving of the car and work with mechanisms.

In spite of the fact that пароксетин does not strengthen a negative impact of alcohol on psychomotor functions, it is not recommended to apply at the same time пароксетин and alcohol.

Side effects:

Frequency and intensity of some listed below side effects of a paroksetin can decrease in process of treatment continuation, and such effects usually do not demand drug withdrawal. Side effects are stratified below on systems of bodies and frequency. Gradation of frequency following: very frequent (> 1/10), frequent (> 1/100, <1/10) infrequent (> 1/1000, <1/100), rare (> 1/10 000, <1/1000) and very rare (<1/10 000), including separate cases. Occurrence of frequent and infrequent side effects was defined on the basis of the generalized data on safety of drug on more than 8000 patients participating in clinical tests it was counted on a difference between the frequency of side effects in group of a paroksetin and in group of placebo. Occurrence of rare and very rare side effects was defined on the basis of post-marketing data, and it concerns rather a frequency of messages on such effects, than the true frequency of effects.

From system of a hemopoiesis: infrequent - abnormal bleeding, hemorrhage in skin and mucous membranes is preferential (most often - bruises); very rare - thrombocytopenia.

From immune system: very rare - allergic reactions (including a small tortoiseshell and a Quincke's disease).

From endocrine system: very rare - a syndrome of disturbance of secretion of ADG.

Metabolic disturbances and disturbances of food: frequent - a loss of appetite, increase in level of cholesterol; rare - a hyponatremia. The hyponatremia occurs preferential at elderly patients and can be caused by a syndrome of disturbance of secretion of ADG.

Mental disorders: frequent - drowsiness, sleeplessness, agitation, unusual dreams (including dreadful dreams); infrequent - confusion of consciousness, a hallucination; rare - maniacal reactions. These symptoms can be also caused actually by a disease.

From a nervous system: frequent - dizziness, a tremor, a headache; infrequent - extrapyramidal frustration; rare - spasms, an akathisia, a syndrome of uneasy legs; very rare - a serotoninovy syndrome (symptoms can include agitation, confusion of consciousness, the strengthened sweating, hallucinations, a hyperreflexia, a myoclonus, tachycardia with a shiver and a tremor). At patients with disturbance of motive functions or receiving neuroleptics seldom it was reported about development of extrapyramidal symptomatology, including oro-facial dystonia.

From an organ of sight: frequent - a sight illegibility; infrequent - a mydriasis; very rare - acute glaucoma.

From cardiovascular system: infrequent - sinus tachycardia, postural hypotonia.

From respiratory system: frequent - yawning.

From the alimentary system: very frequent - nausea; frequent - a lock, diarrhea, vomiting, dryness in a mouth; very rare - gastrointestinal bleeding.

Gepatobiliarny disturbances: rare - increase in level of liver enzymes; very rare - the hepatitis which sometimes is followed by jaundice and/or a liver failure. Increase in levels of liver enzymes is sometimes observed. Post-marketing messages on damages of a liver (such as hepatitis, sometimes with jaundice, and/or a liver failure) are very rare. The issue of expediency of the termination of treatment paroksetiny needs to be resolved when long increase in indicators of functional hepatic trials takes place.

From skin and hypodermic fabrics: frequent - perspiration; infrequent - skin rashes; very rare - photosensitivity reactions, heavy skin reactions (including a mnogoformny erythema, Stephens-Johnson's syndrome and a toxic epidermal necrolysis).

From an urinary system: rare - an urination delay, an urine incontience.

From reproductive system and mammary glands: very frequent - sexual dysfunction; rare - гиперпролактинемия / a galactorrhoea.

Others: frequent - an adynamy, increase in body weight; very rare - peripheral hypostases.

The symptoms arising at the treatment termination paroksetiny

Frequent: dizziness, touch disturbances, sleep disorders, alarm, headache.

Infrequent: agitation, nausea, tremor, confusion of consciousness, perspiration, diarrhea.

As well as at cancellation of many psychotropic medicines, the treatment termination paroksetiny (especially sharp) can cause such symptoms as dizziness, touch disturbances (including paresthesias, feeling of the category of electric current and a sonitus), sleep disorders (including bright dreams), agitation or alarm, nausea, a headache, a tremor, confusion of consciousness, diarrhea and perspiration. At most of patients these symptoms are easy or moderately expressed and pass spontaneously. Any group of patients which would be exposed to the increased risk of emergence of such symptoms is not known; therefore if in treatment paroksetiny there is no need any more, its dose needs to be reduced slowly to full drug withdrawal.

The undesirable phenomena observed in clinical trials at children

In clinical trials at children the listed below side effects arose at 2% of patients and met in group of a paroksetin twice more often than in group of placebo: emotional lability (including infliction of harm to, suicide thoughts, suicide attempts, tearfulness and mood swings), hostility, a loss of appetite, a tremor, perspiration, a hyperkinesia and agitation. Suicide thoughts and suicide attempts were generally observed in clinical trials at teenagers with big depressive frustration at which efficiency of a paroksetin is not proved. Hostility was noted at children with obsessivno-compulsive frustration, in particular at children 12 years are younger. Symptoms of cancellation of a paroksetin (emotional lability, nervousness, dizziness, nausea and an abdominal pain) were registered at 2% of patients against the background of a dose decline of a paroksetin or after its full cancellation and met twice more often than in group of placebo.

Interaction with other medicines:

Serotonergic drugs

Use of a paroksetin, as well as other drugs of the SIOZS group, along with serotonergic drugs (including L-tryptophane, triptanes, трамадол, SIOZS group drugs, fentanyl, lithium and the vegetable means containing the St. John's Wort which is made a hole) can cause the effects connected with 5-HT (a serotoninovy syndrome). Use of a paroksetin with MAO inhibitors (including линезолид, the antibiotic which is transformed to the MAO non-selective inhibitor) is contraindicated.

Pimozidum

In a research of a possibility of combined use of a paroksetin and Pimozidum in a low dose (2 mg once) increase in level of Pimozidum was registered. This fact is explained by the known property of a paroksetin to oppress the CYP2D6 system. Owing to a narrow therapeutic index of Pimozidum and its known ability to extend QT interval, combined use of Pimozidum and paroksetin is contraindicated. When using of the specified drugs with paroksetiny it is necessary to be careful and carry out careful clinical monitoring to combinations.

The enzymes participating in metabolism of medicines

Metabolism and pharmacokinetics of a paroksetin can change under the influence of induction or inhibition of enzymes which participate in metabolism of medicines.

When using a paroksetin at the same time inhibitor of the enzymes participating in metabolism of medicines it is necessary to estimate expediency of use of the dose of a paroksetin which is in the lower part of range of therapeutic doses. The initial dose of a paroksetin does not need to be adjusted if it is applied along with drug which is the known inductor of the enzymes participating in metabolism medicinal means (for example, carbamazepine, rifampicin, phenobarbital, Phenytoinum). Any subsequent correction of a dose of a paroksetin has to be defined by its clinical effects (portability and efficiency).

Fosamprenavir/ritonavir

Combined use of a fosamprenavira/ritonavir with paroksetiny led to considerable decrease in concentration of a paroksetin in a blood plasma.

Any subsequent correction of a dose of a paroksetin has to be defined by its clinical effects (portability and efficiency).

Protsiklidin

Daily reception of a paroksetin significantly increases concentration of a protsiklidin in a blood plasma. At emergence of anticholinergic effects the dose of a protsiklidin should be lowered.

Anticonvulsant drugs: carbamazepine, Phenytoinum, sodium Valproatum.

Simultaneous use of a paroksetin and the specified drugs does not influence their pharmacokinetics and a pharmacodynamics at patients with epilepsy.

Ability of a paroksetin to oppress CYP2D6 enzyme

As well as other antidepressants, including other drugs of the SIOZS group, пароксетин the CYP2D6 liver enzyme relating to system of P450 cytochrome oppresses. Oppression of CYP2D6 enzyme can lead to increase in concentration in plasma of at the same time used drugs which are metabolized by this enzyme. Tricyclic antidepressants (for example, amitriptyline, нортриптилин, Imipraminum and desipramine), neuroleptics of a fenotiazinovy row (Perfenazinum and thioridazine), рисперидон, атомоксетин, some antiarrhytmic means of a class 1 C (for example, пропафенон and флекаинид) and метопролол belong to such drugs.

Use of a paroksetin who oppresses the CYP2D6 system can lead to decrease in concentration of its active metabolite - the endoxyhair dryer in a blood plasma, and as a result, to reduce efficiency of Tamoxifenum.

Ability of a paroksetin to oppress CYP3A4 enzyme

The research of interaction in vivo at simultaneous use, in the conditions of an equilibrium state, a paroksetin and a terfenadin which is CYP3A4 enzyme substrate showed what пароксетин does not influence pharmacokinetics of a terfenadin. In a similar research of interaction in vivo influence of a paroksetin on pharmacokinetics of an alprazolam and vice versa was not revealed. Simultaneous use of a paroksetin with terfenadiny, alprazolamy and other drugs which serve as CYP3A4 enzyme substrate can hardly do harm to the patient.

Clinical trials showed that absorption and pharmacokinetics of a paroksetin does not depend or practically does not depend (i.e. the existing dependence does not demand change of a dose) from food, antacids, digoxin, propranolol, alcohol (пароксетин does not strengthen a negative impact of ethanol on psychomotor functions, nevertheless, it is not recommended to accept at the same time пароксетин and alcohol).

Contraindications:

— the combined use of a paroksetin with MAO inhibitors and methylene blue. Paroksetin it is not necessary to apply along with MAO inhibitors or within 2 weeks after their cancellation. It is impossible to appoint MAO inhibitors within 2 weeks after the end of treatment paroksetiny;

— the combined use with thioridazine. Paroksetin it is not necessary to appoint in a combination with thioridazine as he, as well as other drugs oppressing activity of CYP450 2D6 liver enzyme пароксетин can increase concentration of thioridazine in plasma that can lead to lengthening of an interval of QT and the arrhythmia connected with it "pirouette" (torsade de pointes) and sudden death;

— the combined use with Pimozidum;

— use for children and teenagers is younger than 18 years. Controlled clinical trials of a paroksetin at treatment of a depression at children and teenagers did not prove it to efficiency therefore drug is not shown for treatment of the specified age group. Safety and efficiency of a paroksetin were not studied at use for patients of younger age category (7 years are younger);

— hypersensitivity to a paroksetin and other components of drug.

 

Use of the drug PAKSIL® at pregnancy and feeding by a breast

Researches on animals did not reveal at a paroksetin of teratogenic or selective embriotoksichesky activity.

The last epidemiological researches of result of pregnancy at reception of antidepressants in the I trimester revealed increase in risk of the congenital anomalies, in particular, cardiovascular system (for example, defects of interventricular and interatrial partitions) connected with reception of a paroksetin. By data occurrence of defects of cardiovascular system at use of a paroksetin during pregnancy is approximately equal 1/50 whereas the expected occurrence of such defects is approximately equal in the general population 1/100 newborns.

At purpose of a paroksetin it is necessary to consider the possibility of alternative treatment at pregnant women and women planning pregnancy. Women who received during pregnancy пароксетин have messages on premature births or other drugs of group of the selective serotonin reuptake inhibitors (SSRI), however relationship of cause and effect between these drugs and premature births is not established. Paroksetin it is not necessary to apply during pregnancy if his potential advantage does not exceed possible risk.

It is necessary to watch the state of health of those newborns whose mothers accepted пароксетин on late durations of gestation as the newborns who were affected by a paroksetin or other drugs of the SIOZS group in the III trimester of pregnancy have messages on complications especially attentively. It should be noted, however, as in this case relationship of cause and effect between the mentioned complications and this medicamentous therapy is not established. The described clinical complications included: respiratory distress syndrome, cyanosis, apnoea, convulsive attacks, instability of temperature, difficulty with feeding, vomiting, hypoglycemia, arterial hypertension, hypotension, hyperreflexia, tremor, shiver, nervous irritability, irritability, lethargy, constant crying and drowsiness. In some messages symptoms were described as neonatal manifestations of a withdrawal. In most cases the described complications arose right after childbirth or soon after them (<24 h). According to epidemiological researches administration of drugs of the SIOZS group (including пароксетин) on late durations of gestation is accompanied by increase in risk of development of persistent pulmonary hypertensia of newborns. The increased risk is observed at the children born from mothers accepting SIOZS on late durations of gestation by 4-5 times exceeds observed in the general population (1-2 on 1000 cases of pregnancy).

Insignificant quantities of a paroksetin get into breast milk. Nevertheless, пароксетин it is not necessary to accept during breastfeeding unless the advantage of therapy for mother exceeds potential risks for the child.

Fertility

SIOZS (including пароксетин) can influence quality of semen. This effect is reversible after drug withdrawal. Change of properties of sperm can entail fertility disturbance.

 

Use at abnormal liver functions

At patients with the expressed abnormal liver functions the dose of drug should be reduced to the lower bound of range of doses.

 

Use at renal failures

At patients with the expressed renal failures (KK less than 30 ml/min.) a dose of drug should be reduced to the lower bound of range of doses.

 

Use for elderly patients

At patients of advanced age treatment should be begun with a dose for adults, further the dose can be increased to 40 mg /

 

Use for children

Treatment by antidepressants of children and teenagers with big depressive frustration and other mental diseases, is associated with the increased risk of emergence of suicide thoughts and suicide behavior.

In clinical tests the undesirable phenomena connected with a suitsidalnost (suicide attempts and suicide thoughts) and hostility (preferential aggression, deviant behavior and anger), were more often observed at the children and teenagers receiving пароксетин than at those patients of this age group who received placebo. Now there are no data on long-term safety of a paroksetin for children and teenagers who would concern influence of drug on growth, maturing, cognitive and behavioral development.

As a result of clinical trials at children and teenagers occurrence of the undesirable phenomena at cancellation of a paroksetin made 32% whereas occurrence of the undesirable phenomena in group of placebo made 24%.

Overdose:

Objective and subjective symptoms: the available information on overdose of a paroksetin confirms its broad range of safety. At overdose of a paroksetin in addition to the symptoms described in the section "Side effect" fever, changes of the ABP, involuntary reductions of muscles, alarm and tachycardia are observed.

The condition of patients was usually normalized without serious effects even at one-time reception of doses to 2000 mg. In a number of messages such symptoms as a coma and changes of an ECG are described, cases of death were very rare, usually in those situations when patients accepted пароксетин together with other psychotropic drugs or with alcohol.

Treatment: the specific antidote of a paroksetin does not exist. Treatment has to consist of the general measures applied at overdose of any antidepressants. The maintenance therapy and frequent monitoring of the main physiological indicators is shown. Treatment of the patient has to be carried out according to a clinical picture or according to recommendations of the national toxicological center.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 30 °C. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

10 - blisters (1) - packs cardboard.
10 - blisters (3) - packs cardboard.
10 - blisters (10) - packs cardboard.