PAX

Active material: Paroxetine
When ATH: N06AB05
CCF: Antidepressant
ICD-10 codes (testimony): F31, F32, F33, F40, F41.0, F41.1, F41.2, F42, F43
When CSF: 02.02.04
Manufacturer: GlaxoSmithKline({France)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills white, coated, Oval, lenticular, Engraved “20” on one side and a fault line – another.

Excipients: calcium dihydrophosphate dihydrate, sodium carboxykrahmal type A, magnesium stearate.

The composition of the shell: gipromelloza, Titanium dioxide, macrogol 400, polysorbate 80.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

Antidepressant. Belongs to the group of selective inhibitors of the reverse capture of serotonin.

The mechanism of action of Paxil is based on its ability to select a reverse capture of serotonin (5-hydroxitryptamine /5-ant) Porenaptic membrane, What is the reason for the increase in the free content of this neurotransmitter in the synaptic gap and the strengthening of serotonergic action in the central nervous system, responsible for the development of thymoanaleptic (antidepressant) effect.

Paroxetine has low affinity to m-cholinoreceptors (It has a weak anticholinergic action), a₁-, a₂– and β-adrenergic receptors, as well as dopaminov (D₂), 5-HT₁-Similar, 5-HT₂-Similar and histamine h₁-Receptor.

According to a study of behavior and EEG, paroxetine reveals weak activating properties, when it is prescribed in doses above those, which are necessary to inhibit the capture of serotonin. Paroxetine does not affect the cardiovascular system, does not violate psychomotor functions, The central nervous system does not depress. In healthy volunteers, it does not cause a significant change in the level of blood pressure, Heart rate and EEG.

The main components of the profile of psychotropic activity of the Paxil are antidepressant and anti -aircraft effects. Paroxetine can cause weak activating effects in doses, exceeding those, which are required to inhibit the reverse capture of serotonin.

In the treatment of depressive disorders, paroxetine demonstrated the effectiveness, comparable to the effectiveness of tricyclic antidepressants. There is evidence, that paroxetine has therapeutic effectiveness even in those patients, who did not respond adequately to the previous standard therapy with antidepressants. The condition of patients improves through 1 A week after the start of treatment, but exceeds the effectiveness of placebo only on 2 week. The morning intake of paroxetine does not have a negative effect on the quality and duration of sleep. Besides, With effective therapy, sleep may improve. During the first few weeks of taking paroxetine improves the condition of patients with depression and suicidal thoughts.

The results of the research, in which patients took parksetin during 1 year, shown, that the drug effectively prevents depression relapses.

With panic disorder, the purpose of the paxil in combination with drugs, improving cognitive functions and behavior, It turned out to be more effective, than monotherapy with drugs, improving cognitive-behavioral function, which is aimed at their correction.

Pharmacokinetics

Absorption

After oral administration of paroxetine is well absorbed from the gastrointestinal tract. Eating does not affect the absorption.

Distribution

C_ss set to 7-14 day since the start of therapy. Clinical effects of paroxetine (Side effect and effectiveness) do not correlate with its concentration in plasma.

Paroxetine extensively distributed in the tissues, and pharmacokinetic calculations show, What only 1% It is present in plasma, Moreover, in therapeutic concentrations 95% – In the form associated with proteins.

Established, that paroxetine in small quantities stands out with breast milk, and also penetrates through the placental barrier.

Metabolism

The main metabolites of paroxetine are polar and conjugated oxidation and methylation products. Due to the low pharmacological activity of metabolites, their effect on the therapeutic effectiveness of the drug is unlikely.

Since paroxetine metabolism includes the stage “first pass” through the liver, Its number, defined in system circulation, less, which is absorbed from the gastrointestinal tract. With an increase in the dose of paroxetine or with multiple dosing, when the load on the body increases, partial absorption of the effect occurs “first pass” Through the liver and decrease in plasma clearance of paroxetine. As a result, there may be an increase in the concentration of paroxetine in plasma and fluctuations in pharmacokinetic parameters, What can only be observed in those patients, In which, when taking low doses, low levels of the drug in plasma are achieved.

Deduction

Excreted in the urine (in unchanged form – less 2% doses and in the form of metabolites – 64%) Or with bile (in unchanged form – 1%, as metabolites – 36%).

T_1/2 Vary, However, on average it is 16-24 no.

The excretion of paroxetine is biphase, including primary metabolism (The first phase) and the following system elimination.

With prolonged continuous use of the drug, the pharmacokinetic parameters do not change.

Pharmacokinetics in special clinical situations

In elderly patients, the concentration of paroxetine in plasma is increased, And the range of plasma concentrations almost coincides with the range of healthy adult volunteers.

In patients with severely impaired renal function (CC less than 30 ml / min) and in patients with impaired liver function, the concentration of paroxetine in plasma is increased.

Testimony

- Depression of all types, including reactive depression and severe depression, depression, accompanied by anxiety (Research results, in which patients received the drug during 1 year, show, that it is effective in the prevention of relapse of depression);

— treatment (incl. Supporting and preventive therapy) obsessive-compulsive disorder (OCD). Besides, Paroxetine is effective in the prevention of relapse of the OKR;

— treatment (incl. Supporting and preventive therapy) panic disorder with and without and without it. Besides, Paroxetine is effective in the prevention of relapse of panic disorder;

— treatment (incl. Supporting and preventive therapy) social phobia;

— treatment (incl. Supporting and preventive therapy) generalized alarming disorder. Besides, Paroxetine is effective in the prevention of relapses of this disorder;

- Treatment of post -traumatic stress disorder.

Dosage regimen

To Adult at depression average therapeutic dose is 20 mg / day. With insufficient efficiency, the dose can be increased to maximum 50 mg / day. An increase in the dose should be carried out gradually – on 10 mg at intervals of 1 week. The effectiveness of therapy should be evaluated and, if necessary, adjust the dose of paxil through 2-3 weeks after the start of therapy and further depending on clinical indications.

To stop the depression and relapse of relapse, it is necessary to observe the duration of the corresponding therapy. This period can be several months.

To Adult at obsessive-compulsive disorder average therapeutic dose is 40 mg / day. You should start treatment with 20 mg / day, then gradually the dose increases by 10 mg weekly. With an insufficient clinical effect, the dose can be increased to 60 mg / day. It is necessary to observe the adequate duration of therapy (several months).

To Adult at Panic disorder average therapeutic dose is 40 mg / day. Treatment should begin using the drug in a dose 10 mg / day. The drug is used in a low initial dose in order to minimize the possible risk of exacerbation of panic symptoms, which can be observed at the initial stage of therapy. Subsequently, the dose is increased by 10 MG weekly until the effect is obtained. With insufficient efficiency, the dose can be increased to 60 mg / day. It is necessary to observe the adequate duration of therapy (several months and longer).

To Adult at social phobia average therapeutic dose is 20 mg / day. With an insufficient clinical effect, the dose can be increased gradually by 10 MG weekly before 50 mg / day.

To Adult at generalized anxiety disorder average therapeutic dose is 20 mg / day. With an insufficient clinical effect, the dose can be increased gradually by 10 MG weekly to the maximum dose 50 mg / day.

To Adult at post -traumatic stress disorder average therapeutic dose is 20 mg / day. With an insufficient clinical effect, the dose can be increased gradually by 10 MG weekly as possible to 50 mg / day.

In elderly patients Treatment should begin with a dose for adults, In the future, the dose can be increased to 40 mg / day.

In patients with severely impaired renal function (CC less than 30 ml / min) and in patients with function disorders The liver is prescribed dose, in the lower part of the therapeutic dose range.

Paxil is taken 1 Once/day in the morning with meals. Tablets should be swallowed whole, without chewing, drinking water.

Cancel the drug

Avoid abrupt discontinuation of therapy. The daily dose should be reduced by 10 MG weekly. After reaching a daily dose 20 MG patients continue to take this dose for a week and after that the drug is completely canceled.

If the symptoms of cancellation develop during a dose decrease or after the cancellation of the drug, It is advisable to resume the reception of a previously assigned dose. Subsequently, the dose of the drug should be reduced, but more slowly.

Side effect

The frequency and intensity of some side effects can decrease as therapy continues and usually does not lead to the cessation of treatment. The following criteria were used to assess the incidence of adverse events: Often (>1/10), often (>1/100 and <1/10), infrequently (>1/1000 and <1/100), rarely (>1/10 000 and <1/1000), rarely (<1/10 000), including individual cases. The encountered frequent and infrequent side effects was determined on the basis of generalized data on the safety of the drug more than 8000 man, participating in clinical trials (It was read by the difference between the frequency of side effects in the paroxetine group and in the placebo group). Occurrence of rare and very few side effects were determined based on post-marketing data (It concerns the frequency of messages about such effects, than the true frequency effects themselves).

From the digestive system: Often – nausea; often – decreased appetite, dry mouth, constipation, diarrhea; rarely – elevated liver enzymes; rarely – gastrointestinal bleeding, hepatitis (Sometimes with jaundice), hepatic failure. Post -marketing messages about liver damage are very rare. With the development of side effects from the liver, the question of the advisability of cessation of therapy should be solved in cases, when there is a long increase in functional samples.

CNS: often – drowsiness, insomnia, ažitaciâ, tremor, dizziness, headache; infrequently – confusion, hallucinations, extrapyramidal symptoms; rarely – mania, convulsions, akathisia; rarely – serotonin syndrome (ažitaciâ, confusion, Diaforez, hallucinations, hyperreflexia, myoclonus, tachycardia, tremor). In patients with motor disorders or taking antipsychotics – Extrapyramidal disorders with oropharative dystonia. Some of the symptoms (drowsiness, insomnia, ažitaciâ, confusion, hallucinations, mania) may be due to the underlying disease.

On the part of the organ of vision: often – blurred vision; infrequently – midriaz; rarely – ostraya glaucoma.

Cardio-vascular system: infrequently – sinus tachycardia; infrequently – Postural hypotension.

From the urinary system: rarely – urinary retention, urinary incontinence.

From the blood coagulation system: infrequently – Hemorrhages in the skin and mucous membranes, bruising; rarely – thrombocytopenia.

On the part of the endocrine system: rarely – inappropriate secretion of antidiuretic hormone; rarely – Hypoprolactinemia/Galactorrhea.

Metabolism: rarely – giponatriemiya (Mostly in elderly patients), which is sometimes due to the syndrome of insufficient secretion of antidiuretic hormone.

Allergic reactions: rarely – angioedema, hives.

Dermatological reactions: often – increased sweating; infrequently – skin rash; rarely – photosensitivity reaction.

Other: Often – sexual dysfunction; often – Improving cholesterol levels, zevota, asthenia, weight gain; rarely – peripheral edema.

After the cancellation of the drug often Dizziness is noted, sensory violation, sleep disorders, alarm, headache, infrequently – ažitaciâ, nausea, tremor, confusion, increased perspiration, diarrhea.

Unwanted symptoms, observed during clinical trials in children

In clinical trials in children, side effects listed below occurred in 2% patients and met in 2 times more likely, than placebo: emotional lability (incl. harm to oneself, suicidal thoughts, suicide attempts, tearfulness, mood lability), hostility, decreased appetite, tremor, increased perspiration, Hyperkinesia and agitation. Suicidal thoughts, Suicidal attempts were mainly observed in clinical trials in adolescents with a pronounced depressive disorder, in which the effectiveness of paroxetine is not proven. Hostility was noted in children (especially aged age 12 years) with obsessive-compulsive disorder.

Contraindications

- Simultaneous reception of MAO inhibitors and the period 14 days after their cancellation (MAO inhibitors cannot be prescribed during 14 days after the end of treatment with parksetin);

- simultaneous intake of thioridazine;

- simultaneous intake of pimoside;

- Up to 18 years (Controlled clinical studies of paroxetine in the treatment of depression in children and adolescents have not proved its effectiveness, Therefore, the drug is not indicated for the treatment of this age group). Paroxetine is not prescribed for children aged to 7 years due to the lack of security and efficiency of use of the drug in this category of patients.

- increased sensitivity to paroxetine and other components of the drug.

Pregnancy and lactation

IN experimental studies no teratogenic or embryotoxic effect of paroxetine has been detected.

Recent epidemiological studies of pregnancy outcomes when taking antidepressants in the first trimester revealed an increase in the risk of congenital anomalies, in particular, Cardiovascular (eg, Defects of the interventricular and atrial partitions), associated with paroxetine. According to data, defects in the cardiovascular system when using paroxetine during pregnancy is approximately equal 1/50, Whereas the expected encounter of such defects in the general population is approximately equal 1/100 Newborn. When prescribing paroxetine, it is necessary to consider the possibility of alternative treatment in pregnant and pregnant women planning women.

There are reports of premature birth in women, who received paroxetine during pregnancy, However, a causal relationship with taking the drug has not been established. Paxil should not be used during pregnancy, except, when the potential benefit of treatment exceeds possible risk, drug-related.

It is necessary to especially carefully monitor the health status of those newborn, whose mothers were received by paroxetine in late pregnancy, since there are reports of complications in newborns, exposure to paroxetine or other drugs of the group of selective inhibitors of the reverse capture of serotonin in the 3rd trimester of pregnancy. It should be noted, However, that in this case, the causal relationship between the mentioned complications and this drug therapy has not been established. The described clinical complications included: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, difficulty feeding, vomiting, gipoglikemiû, hypertension, gipotenziю, hyperreflexia, tremor, tremor, nervous excitability, irritability, lethargy, constant crying and drowsiness. In some messages, symptoms were described as neonatal manifestations of cancellation syndrome. In most cases, the described complications occurred immediately after childbirth or shortly after them (less 24 no). According to one epidemiological study, taking the drugs of selective inhibitors of the reverse capture of serotonin (Including paroxetine) In the duration of pregnancy later 20 Weeks are associated with an increase in the risk of developing Persian pulmonary hypertension of newborn. Absolute risk among patients, taking selective inhibitors of the reverse capture of serotonin in late pregnancy, is about 6-12 on 1000 Women, compared with 1-2 on 1000 women in a common population.

Minor paroxetine penetrates into breast milk. Nonetheless, Paroxetine should not be taken during breastfeeding, except, when its benefit for the mother exceeds potential risks for the child.

Cautions

Young patients, especially with great depressive disorder, I can be at increased risk of suicidal behavior during the treatment of paroxetin. Analysis of placebo-controlled studies in adults with mental illness, indicates an increase in the frequency of suicidal behavior in young patients (aged 18-24 years) Against the background of taking paroxetine compared to the placebo group (2.19% to 0.92% respectively), although this difference is not considered statistically significant. In patients of older age groups (from 25 to 64 and older 65 years) there was no increase in the frequency of suicidal behavior. In adults of all age groups with a large depressive disorder, There was a statistically significant increase in cases of suicidal behavior against the background of the treatment of paroxetin compared to the placebo group (The meeting of suicidal attempts 0.32% to 0.05% respectively). However, most of these cases are against the background of paroxetine (8 from 11) was registered in young patients from the age of 18-30 years. Data, obtained in a study in patients with a large depressive disorder, may indicate an increase in the frequency of cases of suicidal behavior in patients younger 24 years with various mental disorders.

In patients with depression, exacerbation of the symptoms of the disease and/or the appearance of suicidal thoughts and suicidal behavior (suicidality) can be observed regardless of that, whether they receive antidepressants. This risk persists until, until a pronounced remission is reached. Improving the patient's condition may be absent in the first weeks of treatment and more, Therefore, the patient must carefully observe the timely detection of the clinical exacerbation of the tendency to suicide, especially at the beginning of treatment, as well as during periods of dose changes (increase or decrease). The clinical experience of the use of all antidepressants shows, that the risk of suicide can increase in the early stages of recovery.

Other mental disorders, For the treatment of which paroxetine is used, can also be associated with an increased risk of suicidal behavior. Besides, These disorders can be comorbid states, accompanying a large depressive disorder. Therefore, in the treatment of patients with other mental disorders, the same precautions should be observed, as in the treatment of a large depressive disorder.

The greatest risk of suicidal thoughts or suicidal attempts are patients, having suicidal behavior or suicidal thoughts, Young patients, as well as patients with pronounced suicidal thoughts before the start of treatment, And therefore, all of them need to pay special attention during treatment. Patients (and staff) It is necessary to warn about the need to monitor the worsening of their condition and/or the appearance of suicidal thoughts/suicidal behavior or thoughts about causing harm during the entire course of treatment, especially at the beginning of treatment, During the dose of the drug (Increase and decrease). In the event of these symptoms, it is necessary to immediately seek medical help.

It must be remembered, that such symptoms as agitation, Acatisia or mania can be associated with the underlying disease or is a consequence of the therapy used. In case of symptoms of clinical deterioration (Including new symptoms) and/or suicidal thoughts/behavior, especially with their sudden appearance, the increase in the severity of manifestations, or in that case, If they were not part of the previous symptom complex in this patient, It is necessary to reconsider the treatment regime until the cancellation of the drug.

Sometimes the treatment of parksetin or another drug of the group of selective inhibitors of the reverse capture of serotonin is accompanied by the occurrence of acathizia, which is manifested by a sense of inner anxiety and psychomotor excitement, when the patient cannot sit quietly or stand; With akatizia, the patient usually experiences subjective discomfort. The probability of acathizia is the highest in the first few weeks of treatment.

In rare cases, against the background of paroxetine treatment, serotonin syndrome or symptoms may occur, like malignant antipsychotic syndrome (hyperthermia, muscle rigidity, myoclonus, Vegetative disorders with possible rapid changes in the indicators of vital functions, altered mental status, including confusion, irritability, Extremely severe agitation, progressive to delirium and coma), Especially if paroxetine is used in combination with other serotonergic drugs and/or antipsychotics. These syndromes pose a potential threat to life, Therefore, in case of their occurrence, treatment with parksetin must be stopped and begin to support symptomatic therapy. Paroxetine should not be prescribed in combination with the predecessors of serotonin (Such as L-tripthophanes, from an oxythriyp) Due to the risk of the development of serotonin syndrome.

A large depressive episode can be the initial manifestation of bipolar disorder. It is considered (although this is not proved by controlled clinical trials), that the treatment of such an episode with an antidepressant alone can increase the likelihood of accelerated development of a mixed/manic episode in patients, risk of bipolar disorder.

Before starting treatment, an antidepressant, it is necessary to conduct a thorough screening to assess the risk of a bipolar disorder in this patient; Such screening should include the collection of detailed psychiatric history, including data on the presence of suicide cases in the family, bipolar disorder and depression.

Paroxetine is not registered for the treatment of a depressive episode as part of a bipolar disorder. Paroxetine should be used with caution in patients, a history of mania.

Paroxetine treatment should begin carefully, no earlier than 2 weeks after stopping therapy with MAO inhibitors; The dose of paroxetine must be increased gradually until the optimal therapeutic effect is achieved.

Caution is recommended to be caused by paroxetine patients with severe impaired renal function and patients with impaired liver function.

As with other antidepressants, paroxetine should be used with caution in patients with epilepsy. The frequency of convulsive seizures in patients, taking paroxetine, is less than 0.1%. In the event of a convulsive seizure, treatment with parksetin must be stopped.

There is only a limited experience in the simultaneous use of paroxetine and electricity therapy.

Paroxetine vыzыvaet mydriasis, and it must be used with caution in patients with closed -angled glaucoma.

In the treatment of paroxetin, hyponatremia rarely occurs and mainly in elderly patients and is leveled after the cancellation of paroxetine.

It was reported about hemorrhages in the skin and mucous membranes (including gastrointestinal bleeding) patients, taking parksetin. Therefore, paroxetine should be used with caution in patients, which simultaneously receive drugs, increasing the risk of bleeding, in patients with a certain tendency to bleeding and in patients with diseases, predisposing to bleeding.

In the treatment of patients with heart diseases, ordinary precautions should be observed.

As a result of clinical studies in adults, the occurrence of undesirable phenomena when canceling paroxetine was 30%, Whereas the incredible phenomena in the placebo group was 20%.

After the cancellation of the drug (Especially harsh) often Dizziness is noted, sensory violation (paraesthesia, noise in ears), sleep disorders (vivid dreaming), alarm, headache, infrequently – ažitaciâ, nausea, tremor, confusion, increased perspiration, diarrhea. In most patients, these symptoms were mild or moderately expressed, but in some patients they can be severe. Typically, cancellation symptoms occur in the first few days after the cancellation of the drug, However, in rare cases – after random pass of one dose. Usually, These symptoms take place on their own within two weeks, but in some patients – to 2-3 months or more. Therefore, it is recommended to gradually reduce the dose of paroxetine (For several weeks or months before its full abolition, depending on the needs of the patient).

The occurrence of symptoms of cancellation does not mean, that the drug causes dependence.

As a result of clinical studies in children and adolescents, the encountered unwanted phenomena when canceling paroxetine was 32% , Whereas the incredible phenomena in the placebo group was 24%.

Children have symptoms of paroxetine cancellation (emotional lability, incl. suicidal thoughts, suicide attempts, Changes of moods and descendability, as well as nervousness, dizziness, nausea and abdominal pain) were observed in 2% patients against the background of a decrease in the dose of paroxetine or after its complete cancellation and met in 2 times more likely, than placebo.

If the paxil -observant increase in the level of hepatic enzymes is persisted for a long time, the drug should be discontinued.

Use in Pediatrics

Treatment with antidepressants of children and adolescents with great depressive disorder and other mental illness, associated with an increased risk of suicidal thoughts and suicidal behavior.

In clinical trials, undesirable phenomena, associated with suicidality (suicidal attempts and suicidal thoughts) and hostility (Mostly aggression, deviant behavior and anger), more often observed in children and adolescents, receiving paroxetines, than those patients of this age group, who received placebo. There is currently no data on the long -term safety of paroxetine for children and adolescents, which would concern the effect of the drug on growth, maturation, cognitive and behavioral development.

Effects on ability to drive vehicles and management mechanisms

Paxil therapy does not cause cognitive disorders or psychomotor inhibition. Nonetheless, As in the treatment of any psychotropic drugs, patients must be careful when driving a car and working with moving mechanisms.

Overdose

The available information about the overdose of parksetin indicates a wide safety range.

Symptoms: Strengthening the side effects described above, as well as vomiting, fever, changes in blood pressure, involuntary muscle contractions, alarm, tachycardia. Patients usually do not develop serious complications even with one -time admission before 2 G Paroxetina. In some cases, a coma develops and changes in EEG, A fatal outcome with a combined use of paroxetine with psychotropic drugs or alcohol is very rare.

Treatment: Standard events, used in an overdose of antidepressants (gastric lavage through artificial vomiting, appointment 20-30 MG activated coal every 4-6 h during the first day after an overdose). Spetsificheskiy antidote unknown. Supporting therapy and control of the vital functions of the body is shown.

Drug Interactions

The use of paroxetine simultaneously with serotoninergic drugs (Including L-tripthophanes, trïptanı, tramadol, Drugs of the group of selective inhibitors of the reverse capture of serotonin, lithium and plant remedies, containing St. John's wort) can cause serotonin syndrome. The use of paroxetine with MAO inhibitors (Including the linema, antibiotic, transforming into a non -selective inhibitor of MAO) contraindicated.

In the study of the possibility of joint use of paroxetine and pimoside in a low dose (2 mg dose) An increase in the level of pimoside was registered. This fact is explained by the property of paroxetine to inhibit the CYP2D6 system. Due to the narrow therapeutic pimoside index and its known ability to lengthen the QT interval, The joint use of pimoside and paroxetine is contraindicated. When using these drugs in combination with paroxetine, care must be observed and careful clinical monitoring must be carried out.

Metabolism and pharmacokinetic parameters of paroxetine can change while using drugs, inducing or inhibitory enzymes, involved in metabolism of drugs.

With the simultaneous use of paxil with drugs, inhibitory enzymes metabolism, The feasibility of using the dose of paroxetine should be evaluated, in the lower part of the therapeutic dose range. With combined use with drugs, inducing enzymes metabolism (Carbamazepine, phenytoin, rifampicin, phenobarbital), no change in the initial doses of Paxil is required. Subsequent dose correction should be carried out depending on the clinical effect (tolerance and effectiveness).

The joint use of fosamprenavir/ritonavir with parksetin led to a significant decrease in the concentration of paroxetine in blood plasma. Any subsequent adjustment of the dose of paroxetine should be determined by its clinical effects (tolerance and effectiveness).

Daily prescription of the paxil significantly increases the level of proscclidine in plasma. In the presence of anticholinergic symptoms, the dose of prosiklidin should be reduced.

With the simultaneous use of paxille with anticonvulsants for epilepsy (Carbamazepine, phenytoin, sodium valproate) no influence on the pharmacokinetics and pharmacodynamics of the last.

Paroxetine depresses the isoenzyme CYP2D6, which can lead to an increase in plasma concentrations simultaneously used, which are metabolized by this enzyme. Such drugs include tricyclic antidepressants (eg, Amitriptyline, nortryptylyn, imipramine and dezipramine), neuroleptics of the phenotiazin series (Perfenazin and thioridase), risperidone, Atomoxetine, some antiarrhythmic means of class 1 FROM (eg, Propafenon and Flekainid) and metoprolol.

The use of paroxetine with Jamoxifen due to the depression of the CyP2D6 isoenzyme can lead to a decrease in the concentration of the active metabolite of customsifen in blood plasma, and as a consequence, Reduce the effectiveness of tamoxifen.

Study of the interaction in vivo while using, in conditions of equilibrium, Paroxetina and Terfenadina, which is the substrate of the enzyme CYP3A4, found, that paroxetine does not affect the pharmacokinetics of terphenin. In a similar study of the interaction of In Vivo, there was no effect of paroxetine on the pharmacokinetics of alpraisolam, and vice versa. Paxil combination with terphenadin, alprazolam and other drugs, which are substrates for the CYP3A4 isoenzyme, does not cause undesirable reactions.

Paroxetine should not be prescribed in combination with thioridazine, Since he, Like other drugs inhibiting the activity of the CYP2D6 isoenzyme, can increase the concentrations of paroxetine AB plasma blood, which can lead to lengthening the QT interval and the development of arrhythmia of the type “pirouette” And sudden death.

With the simultaneous use of short -acting sleeping pills, no additional side effects were noted.

Clinical studies have shown, that the absorption and pharmacokinetics of paroxetine does not depend or practically depend (ie. The existing dependence does not require dose changes) From food, Antacids, digoksina, propranolol, ethanol.

Paroxetine does not enhance the negative effect of ethanol on psychomotor functions, Nonetheless, It is not recommended to take paroxetine and alcohol simultaneously.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.