Paxil instructions for use reviews of doctors. Paxil - official * instructions for use

Antidepressant

Active substance

Release form, composition and packaging

Film-coated tablets white, oval, biconvex, engraved with "20" on one side and a line on the other side.

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

The composition of the film shell: Opadry white YS-1R-7003 * - 7 mg (hypromellose - 4.2 mg, titanium dioxide - 2.2 mg, macrogol 400 - 0.6 mg, polysorbate 80 - 0.1 mg).

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

* when preparing a solution of the Opadry white film casing, purified water is used, which is removed during the drying process.

pharmachologic effect

Mechanism of action

Paroxetine is a potent and selective 5-hydroxytryptamine (5-HT) reuptake inhibitor. Its antidepressant activity and efficacy in the treatment of obsessive-compulsive disorder (OCD) and panic disorder are thought to be due to specific inhibition of 5-HT reuptake in brain neurons.

The chemical structure of paroxetine differs from tricyclic, tetracyclic and other known antidepressants.

Paroxetine has a low affinity for muscarinic cholinergic receptors, and animal studies have shown that it has only weak anticholinergic properties.

In accordance with this selective action of paroxetine, in vitro studies have shown that, unlike tricyclic antidepressants, it is characterized by a slight affinity for α 1 , α 2 and β-adrenergic receptors, as well as for dopamine (D 2), 5-HT 1 - similar, 5-HT 2 and histamine (H 1) receptors. The lack of interaction with postsynaptic receptors in vitro is confirmed by the results of in vivo studies, which indicate that paroxetine does not depress the central nervous system and does not cause arterial hypotension.

Pharmacodynamic properties

Paroxetine does not disrupt psychomotor functions and does not enhance the inhibitory effect of ethanol on the central nervous system.

Like other selective 5-HT reuptake inhibitors, paroxetine causes symptoms of 5-HT receptor overstimulation when administered to animals that have previously received MAO inhibitors or tryptophan.

In behavioral and EEG studies, paroxetine has been shown to produce weak activating effects at doses in excess of those required to inhibit 5-HT reuptake. By nature, its activating properties are not amphetamine-like.

Animal studies have shown good cardiovascular tolerance.

After use in healthy individuals, paroxetine does not cause clinically significant changes in blood pressure, heart rate and ECG.

Research has shown that, unlike antidepressants that inhibit reuptake, paroxetine has a much lower ability to inhibit the antihypertensive properties of guanethidine.

Pharmacokinetics

Suction

After oral administration, paroxetine is well absorbed and undergoes first-pass metabolism.

Due to first-pass metabolism, less paroxetine enters the systemic circulation than is absorbed from the gastrointestinal tract. As the amount of paroxetine in the body increases with a single dose of large doses or with multiple doses of conventional doses, partial saturation of the first-pass metabolic pathway occurs and the clearance of paroxetine from decreases. This leads to a disproportionate increase in plasma concentrations of paroxetine. Therefore, its pharmacokinetic parameters are not stable, resulting in non-linear kinetics. However, the non-linearity of the kinetics is usually weak and is observed only in those patients who, while taking low doses of the drug in plasma, achieve low levels of paroxetine. Steady-state plasma concentrations are reached 7-14 days after initiation of treatment with paroxetine. Its pharmacokinetic parameters are not likely to change during long-term therapy.

Distribution

Paroxetine is widely distributed in tissues, and pharmacokinetic calculations show that only 1% of the total amount of paroxetine present in the body remains in plasma. At therapeutic concentrations, approximately 95% of plasma paroxetine is protein bound.

No correlation was found between plasma concentrations of paroxetine and its clinical effect (i.e., with adverse reactions and efficacy).

Metabolism

The main metabolites of paroxetine are polar and conjugated products of oxidation and methylation, which are easily eliminated from the body. Due to the practical absence of pharmacological activity of these metabolites, their contribution to the therapeutic properties of paroxetine is unlikely.

Metabolism does not limit the ability of paroxetine to selectively act on 5-HT reuptake in neurons.

breeding

Less than 2% of the accepted dose of paroxetine is excreted in the urine unchanged, while the excretion of metabolites reaches 64% of the dose. About 36% of the dose is excreted in the feces, probably entering it with bile; less than 1% of the dose is excreted unchanged in the feces. Thus, paroxetine is eliminated almost completely by metabolism.

Excretion of metabolites is biphasic: at first it is the result of first-pass metabolism, then it is controlled by the systemic elimination of paroxetine.

The half-life of paroxetine varies, but is usually about 24 hours.

Pharmacokinetics in special groups of patients

In elderly patients, patients with severe renal or hepatic insufficiency, the concentration of paroxetine in the blood plasma may increase, but the range of its concentration in the blood plasma coincides with that in healthy adults.

Indications

Depressive episodes of moderate and severe severity

recurrent depressive disorder

The results of studies in which patients took paroxetine for up to 1 year indicate that it is effective in preventing relapse and the return of symptoms of depression.

Obsessive Compulsive Disorder

Paroxetine is effective in the treatment of obsessive-compulsive disorder (OCD), incl. as a means of maintenance and preventive therapy.

In placebo-controlled studies, the efficacy of paroxetine in the treatment of OCD was maintained for at least 1 year. In addition, paroxetine is effective in preventing OCD recurrences.

panic disorder

Paroxetine is effective in the treatment of panic disorder with and without agoraphobia, incl. as a means of maintenance and preventive therapy.

In the treatment of panic disorder, the combination of paroxetine and CBT has been found to be significantly more effective than CBT alone.

In placebo-controlled studies, the efficacy of paroxetine in the treatment of panic disorder was maintained for more than 1 year. In addition, paroxetine is effective in preventing relapses of panic disorder.

social phobia

Paroxetine is effective in the treatment of social phobia, incl. as long-term maintenance and prophylactic therapy. The continued efficacy of paroxetine in the long-term treatment of social phobia has been demonstrated in a relapse prevention study.

Paroxetine is effective in the treatment of generalized anxiety disorder, incl. as long-term maintenance and prophylactic therapy.

The continued efficacy of paroxetine in the long-term treatment of generalized anxiety disorder has been demonstrated in a relapse prevention study.

Paroxetine is effective in the treatment of post-traumatic stress disorder.

Contraindications

- hypersensitivity to paroxetine and any other component that is part of the drug;

- in combination with MAO inhibitors. In exceptional cases (an antibiotic that is a reversible non-selective MAO inhibitor) may be combined with paroxetine, provided that acceptable alternatives to linezolid treatment are not available and the potential benefit of linezolid outweighs the risk of serotonin syndrome or neuroleptic malignant syndrome as a response in the individual patient. Equipment should be available to closely monitor symptoms of serotonin syndrome and monitor blood pressure. Treatment with paroxetine is allowed:

2 weeks after stopping treatment with irreversible MAOIs;

At least 24 hours after stopping treatment with reversible MAO inhibitors (eg, moclobemide, linezolid, methylthioninium chloride (methylene blue));

At least 1 week must elapse between discontinuation of paroxetine and initiation of therapy with any MAO inhibitors;

- in combination with, since, like other drugs that inhibit the activity of the hepatic isoenzyme CYP2D6, paroxetine can increase the concentration of thioridazine in blood plasma. This can lead to prolongation of the QT c interval and the development of associated ventricular arrhythmia of the "pirouette" type and sudden death;

- combined use with pimozide;

- children and adolescents up to 18 years of age. Controlled clinical studies of paroxetine in the treatment of moderate to severe depressive episodes and recurrent depressive disorder in children and adolescents have not proven its effectiveness, therefore paroxetine is not indicated for the treatment of this age group. The safety and efficacy of paroxetine have not been studied in younger patients (less than 7 years of age).

Dosage

Moderate to severe depressive episodes and recurrent depressive disorder

The recommended dose is 20 mg/day. If necessary, the dose may be increased in increments of 10 mg/day up to a maximum dose of 50 mg/day, depending on the clinical response. As with any antidepressant treatment, the effectiveness of therapy should be evaluated and, if necessary, the dose of Paxil should be adjusted 2-3 weeks after the start of treatment and thereafter, depending on clinical indications.

Patients with depression should be treated for a sufficient period of time to achieve an asymptomatic state. This period may be several months.

Obsessive Compulsive Disorder (OCD)

The recommended dose is 40 mg/day. Treatment of patients should begin with a dose of 20 mg/day, which can be increased by 10 mg/day weekly. If necessary, the dose can be increased to a maximum dose of 60 mg / day.

Patients with OCD should be treated for a sufficient period of time to achieve an asymptomatic state. This period may be several months.

panic disorder

The recommended dose is 40 mg/day. Treatment of patients should begin with a dose of 10 mg/day, which can be increased by 10 mg/day weekly, depending on the clinical response. If necessary, the dose can be increased to a maximum dose of 60 mg / day.

Patients with panic disorder should be treated for a sufficient period of time to achieve an asymptomatic state. This period may be several months or more.

social phobia

The recommended dose is 20 mg/day. If necessary, in patients who do not respond when using 20 mg / day, the dose may be increased in increments of 10 mg / day up to a maximum dose of 50 mg / day, depending on the clinical response.

generalized anxiety disorder

Post Traumatic Stress Disorder

Withdrawal of paroxetine

As with other psychotropic drugs, abrupt discontinuation of Paxil should be avoided. The gradual dose reduction scheme used in recent clinical studies was to reduce the daily dose by 10 mg / week. After reaching a dose of 20 mg/day, patients continued to take this dose for 1 week, and only after that the drug was canceled completely. If withdrawal symptoms develop during dose reduction or after discontinuation of the drug, it is advisable to resume taking the previously prescribed dose. Subsequently, the doctor may continue to reduce the dose, but more slowly.

Special patient groups

At elderly patients plasma concentrations of paroxetine may increase, but the range of plasma concentrations is similar to that in younger patients. In this category of patients, therapy should begin with the dose recommended for adults, which can be increased to 40 mg / day.

The plasma concentration of paroxetine is increased in patients with severe renal impairment (CC less than 30 ml / min) or at patients with impaired liver function. Therefore, such patients should be prescribed doses of the drug that are at the lower limit of the therapeutic dose range.

The use of paroxetine in children and teenagers (under 18 years old) contraindicated.

Side effects

The frequency and severity of some of the adverse reactions of paroxetine listed below may decrease with continued treatment, and such reactions usually do not require discontinuation of the drug.

The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is defined as follows: very often (≥1/10), often (≥1/100,<1/10), нечасто (≥1/1000, <1/100), редко (≥1/10 000, <1/1000), очень редко (<1/10 000), включая отдельные случаи, и частота неизвестна. Встречаемость частых и нечастых нежелательных реакций была определена на основании обобщенных данных по безопасности препарата, полученных у более чем 8000 пациентов, участвовавших в клинических исследованиях, показатель рассчитывали по разнице между частотой нежелательных реакций в группе пароксетина и в группе плацебо. Встречаемость редких и очень редких нежелательных реакций определяли на основании пострегистрационных данных, данные показатель в большей степени частоту сообщений о таких реакциях, чем истинную частоту реакций.

From the hematopoietic system: infrequently - pathological bleeding, mainly hemorrhage into the skin and mucous membranes (including ecchymosis); very rarely - thrombocytopenia.

From the immune system: very rarely - severe allergic reactions (including anaphylactoid reactions and angioedema).

From the endocrine system: very rarely - a syndrome of inappropriate ADH secretion.

From the side of metabolism and nutrition: often - loss of appetite, increased cholesterol concentration; rarely - hyponatremia. Hyponatremia occurs predominantly in elderly patients and is sometimes due to the syndrome of inappropriate ADH secretion.

Mental disorders: often - drowsiness, insomnia, agitation, pathological dreams (including nightmares); infrequently - confusion, hallucinations; rarely - manic reactions, anxiety, depersonalization, panic attacks, akathisia; frequency unknown - suicidal thoughts and suicidal behavior. Cases of suicidal thoughts and suicidal behavior have been reported during treatment with paroxetine or early after treatment has been discontinued. These symptoms may also be caused by the disease itself.

From the nervous system: often - dizziness, tremor, headache, impaired concentration; infrequently - extrapyramidal disorders; rarely - convulsions, restless legs syndrome; very rarely - serotonin syndrome (symptoms may include agitation, confusion, increased sweating, hallucinations, hyperreflexia, myoclonus, tachycardia with shivering and tremor). Extrapyramidal symptoms, including orofacial dystonia, have occasionally been reported in patients with impaired motor function or who have used antipsychotics.

From the side of the organ of vision: often - blurred vision; infrequently - mydriasis; very rarely - acute glaucoma.

From the organ of hearing and balance: frequency unknown - tinnitus.

From the side of the cardiovascular system: infrequently - sinus tachycardia, postural hypotension, short-term increase and decrease in blood pressure; rarely - bradycardia. Short-term increases and decreases in blood pressure have been reported following treatment with paroxetine, usually in patients with preexisting hypertension or anxiety.

From the respiratory system: often - yawning.

From the digestive system: very often - nausea; often - constipation, diarrhea, vomiting, dry mouth; very rarely - gastrointestinal bleeding.

From the side of the liver and biliary tract: rarely - increased activity of liver enzymes; very rarely - adverse reactions from the liver (such as hepatitis, sometimes accompanied by jaundice and / or liver failure). An increase in the activity of liver enzymes has been reported. Post-marketing reports of adverse liver reactions (such as hepatitis, sometimes accompanied by jaundice and/or liver failure) have been very rare. The question of the advisability of discontinuing treatment with paroxetine must be addressed in cases where there is a prolonged increase in liver function tests.

From the skin and subcutaneous tissue: often - increased sweating; infrequently - skin rashes, itching; very rarely - photosensitivity reactions, severe skin reactions (including erythema multiforme, Steven-Johnson syndrome and toxic epidermal necrolysis), urticaria.

From the urinary system: infrequently - urinary retention, urinary incontinence.

From the genitals and mammary gland: very often - sexual dysfunction; rarely - hyperprolactinemia, galactorrhea, menstrual disorders (including menorrhagia, metrorrhagia and amenorrhea); very rarely - priapism.

From the musculoskeletal system: rarely - arthralgia, myalgia. Epidemiological studies, mainly conducted in patients aged 50 years and older, have shown an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown.

Others: often - asthenia, weight gain; very rarely - peripheral edema.

Symptoms that occur when treatment with paroxetine is stopped: often - dizziness, sensory disturbances, sleep disturbances, anxiety, headache; infrequently - agitation, nausea, tremor, confusion, increased sweating, emotional lability, visual disturbances, palpitations, diarrhea, irritability.

As with discontinuation of other psychotropic medicinal products, discontinuation of paroxetine treatment (especially abruptly) may cause symptoms such as dizziness, sensory disturbances (including paresthesia, electric shock and tinnitus), sleep disturbances (including vivid dreams), agitation, or anxiety, nausea, headache, tremor, confusion, diarrhea, increased sweating, palpitations, emotional lability, irritability, visual disturbances. In most patients, these symptoms are mild or moderate and resolve spontaneously. No group of patients is known to be at increased risk for such symptoms; therefore, if treatment with paroxetine is no longer necessary, its dose should be reduced slowly until the drug is completely discontinued.

Adverse reactions observed in clinical studies in children

The following adverse reactions have been observed: emotional lability (including self harm, suicidal thoughts, suicide attempts, tearfulness and mood swings), bleeding, hostility, decreased appetite, tremors, increased sweating, hyperkinesia and agitation. Suicidal ideation and suicide attempts have mostly been observed in clinical trials in adolescents with major depressive disorder. Hostility has been reported in children with obsessive-compulsive disorder, especially in children under 12 years of age.

In clinical studies, a gradual decrease in the daily dose (the daily dose was reduced by 10 mg / day at intervals of one week to a dose of 10 mg / day for one week), symptoms such as emotional lability, nervousness, dizziness, nausea and abdominal pain were observed, which were recorded in at least 2% of patients against the background of a reduction in the dose of paroxetine or after its complete withdrawal and occurred at least 2 times more often than in the placebo group.

Overdose

Available information on overdose of paroxetine suggests its wide range of safety.

Symptoms: with an overdose of paroxetine, in addition to the symptoms described in the "Side Effects" section, fever, changes in blood pressure, involuntary muscle contractions, anxiety and tachycardia are observed. The condition of patients usually returned to normal without serious consequences, even with a single dose of up to 2000 mg. A number of reports describe symptoms such as coma and ECG changes; deaths have been very rare, usually reported in situations where patients took paroxetine along with other psychotropic drugs with or without alcohol.

Treatment: no specific antidote for paroxetine is known. Treatment should include general measures for overdose of any antidepressant. Supportive care and frequent monitoring of vital signs and careful monitoring are indicated. The patient should be treated in accordance with the clinical picture or in accordance with the recommendations of the national poison control center, if available.

drug interaction

Serotonergic drugs

The use of paroxetine, as well as other drugs of the SSRI group, simultaneously with serotonergic drugs can cause effects associated with 5-HT receptors (serotonin syndrome). Serotonergic drugs (such as L-tryptophan, triptans, tramadol, SSRIs, lithium, fentanyl, and St.

The simultaneous use of paroxetine with MAO inhibitors (including linezolid, an antibiotic that transforms into a non-selective MAO inhibitor, and methylthioninium chloride (methylene blue)) is contraindicated.

pimozide

In a study of the simultaneous use of paroxetine and pimozide in a single low dose (2 mg), an increase in the level of pimozide was recorded. This fact is explained by the known property of paroxetine to inhibit the CYP2D6 system. Due to the narrow therapeutic index of pimozide and its known ability to prolong the QT interval, the concomitant use of pimozide and paroxetine is contraindicated.

Enzymes involved in drug metabolism

The metabolism and pharmacokinetics of paroxetine may be altered by induction or inhibition of enzymes involved in drug metabolism.

When using paroxetine concomitantly with an inhibitor of enzymes involved in the metabolism of drugs, the use of paroxetine at a dose in the lower part of the therapeutic dose range should be recommended. The starting dose of paroxetine does not need to be adjusted if it is used concomitantly with a drug known to induce drug-metabolizing enzymes (eg, carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent dose adjustment of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Fosamprenavir and ritonavir

Co-administration of fosamprenavir/ritonavir with paroxetine resulted in a significant decrease in paroxetine plasma concentrations. Plasma concentrations of fosamprenavir/ritonavir when co-administered with paroxetine were similar to controls from other studies, indicating no significant effect of paroxetine on the metabolism of fosamprenavir/ritonavir. There are no data on the effect of long-term co-administration of paroxetine with fosamnrenavir/ritonavir. Any subsequent dose adjustment of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Procyclidine

Daily intake of paroxetine significantly increases the concentration of procyclidine in the blood plasma. If anticholinergic effects occur, the dose of procyclidine should be reduced.

Anticonvulsants

The simultaneous use of paroxetine and anticonvulsants (carbamazepine / phenytoin, sodium valproate) does not affect their pharmacokinetic and pharmacodynamic profiles in patients with epilepsy.

Muscle relaxants

SSRI drugs can reduce the activity of plasma cholinesterase, which leads to an increase in the duration of the neuromuscular blocking action of mivacurium and suxamethonium.

The ability of paroxetine to inhibit the CYP2D6 isoenzyme

Like other antidepressants, including other drugs of the SSRI group, paroxetine inhibits the hepatic isoenzyme CYP2D6, which belongs to the cytochrome P450 system. Inhibition of the CYP2D6 isoenzyme can lead to an increase in the plasma concentration of simultaneously used drugs that are metabolized by this enzyme. These drugs include some tricyclic antidepressants (eg, amitriptyline, nortriptyline, imipramine, and desipramine), phenothiazine antipsychotics (perphenazine and thioridazine), risperidone, atomoxetine, some class IC antiarrhythmics (eg, propafenone and flecainide), and metoprolol. The use of paroxetine in combination with metoprolol in heart failure is not recommended due to the narrow therapeutic index of metoprolol for this indication.

Irreversible inhibition of the CYP2D6 system by paroxetine can lead to a decrease in the concentration of endoxifen in the blood plasma and, as a result, reduce the effectiveness of tamoxifen.

Interaction research in vivo with simultaneous use under equilibrium conditions of paroxetine and terfenadine, which is a substrate of the CYP3A4 isoenzyme, showed that paroxetine does not affect the pharmacokinetics of terfenadine. In a similar interaction study in vivo no effect of paroxetine on the pharmacokinetics of alprazolam was found, and vice versa. It is not expected that the simultaneous use of paroxetine with terfenadine, alprazolam and other drugs that are a substrate of the CYP3A4 isoenzyme may be accompanied by a negative effect on the patient.

Drugs that affect the pH of the stomach

Clinical studies have shown that the absorption and pharmacokinetics of paroxetine are independent or practically independent (i.e. the existing dependence does not require dose changes) from:

food intake;

Antacids;

Digoxin;

propranolol;

Alcohol - paroxetine does not enhance the negative effects of ethanol on mental and motor functions, however, it is not recommended to take paroxetine and alcohol at the same time.

Oral anticoagulants

There may be a pharmacodynamic interaction between paroxetine and oral anticoagulants. The combined use of paroxetine and oral anticoagulants may cause an increase in anticoagulant activity and a risk of bleeding. Therefore, paroxetine should be used with caution in patients receiving oral anticoagulants.

NSAIDs and other antiplatelet drugs

There may be a pharmacodynamic interaction between paroxetine and NSAIDs / acetylsalicylic acid. The combined use of paroxetine and NSAIDs / acetylsalicylic acid may increase the risk of bleeding.

Caution should be exercised when treating patients receiving drugs from the SNOZ group concomitantly with oral anticoagulants, drugs that affect platelet function or increase the risk of
bleeding (for example, atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, NSAIDs, COX-2 inhibitors), as well as in the treatment of patients with indications of a history of bleeding disorders or conditions that may cause a predisposition to bleeding.

special instructions

Children and teenagers (under 18)

Paxil should not be used in children and adolescents under 18 years of age.

Antidepressant treatment of children and adolescents with major depressive disorder and other psychiatric illnesses is associated with an increased risk of suicidal thoughts and behavior.

In clinical studies, adverse events associated with suicidal attempts and suicidal thoughts, hostility (predominantly aggression, deviant behavior and anger) were more frequently observed in children and adolescents treated with paroxetine than in patients of this age group who received placebo. At present, there are no data on the long-term safety of paroxetine in children and adolescents regarding the effect of this drug on growth, maturation, cognitive and behavioral development.

Clinical deterioration and suicidal risk in adults

Young patients, especially those with major depressive disorder, may be at increased risk of suicidal behavior during paroxetine therapy. An analysis of placebo-controlled studies in adults with mental illness indicates an increase in the incidence of suicidal behavior in young patients (aged 18-24 years) while taking paroxetine compared with the placebo group: 17/776 (2.19%) vs. 5 / 542 (0.92%) respectively, although this difference is not considered statistically significant. In patients of older age groups (from 25 to 64 years old and over 65 years old), no increase in the frequency of suicidal behavior was observed. In adults of all ages with moderate to severe depressive episodes and recurrent depressive disorder, there was a statistically significant increase in the number of cases of suicidal behavior during treatment with paroxetine compared with the placebo group (frequency of suicide attempts: 11/3455 (0.32%) vs. 1/1978 (0.05%) respectively). However, most of these cases while taking paroxetine (8 out of 11) were registered in young patients aged 18-30 years. Data obtained in a study involving patients with moderate to severe depressive episodes and recurrent depressive disorder may indicate an increase in the incidence of suicidal behavior in young patients, which may persist in patients older than 24 years with various mental disorders.

In patients with depression, exacerbation of symptoms of this disorder and / or the appearance of suicidal thoughts and suicidal behavior (suicidality) can be observed regardless of whether they receive antidepressants. This risk persists until a marked remission is achieved. In general, clinical experience with all antidepressants indicates that the risk of suicide may increase in the early stages of recovery. Other psychiatric disorders for which paroxetine is indicated may also be associated with an increased risk of suicidal behavior, these disorders may also be associated with moderate to severe depressive episodes and recurrent depressive disorder. In addition, patients with a history of suicidal behavior or suicidal thoughts, young patients, and patients with severe suicidal thoughts prior to treatment are at the greatest risk of suicidal thoughts or suicidal attempts. It is necessary to ensure that all patients are monitored for timely detection of clinical deterioration (including new symptoms) and suicidality during the entire course of treatment, especially at the beginning of treatment, or during a change in the dose of the drug (increase or decrease).

It is important for patients (and their caregivers) to be warned to watch for worsening of their condition (including the development of new symptoms) and/or the emergence of suicidal behavior or thoughts of harming themselves. If these symptoms occur, seek immediate medical attention. It must be remembered that the appearance of symptoms such as agitation, akathisia or mania may be associated with both the underlying disease and be a consequence of the therapy used.

If symptoms of clinical deterioration (including the development of new symptoms) and/or suicidal thoughts and/or suicidal behavior occur, especially if they appear suddenly, increase in severity of manifestations, or if the symptoms were not part of the patient's previous symptom complex, it is necessary to reconsider treatment regimen up to drug withdrawal.

Akathisia

In rare cases, treatment with paroxetine or another SSRI drug is accompanied by the development of akathisia, which is manifested by a feeling of internal restlessness and psychomotor agitation when the patient cannot sit or stand still; with akathisia, the patient usually experiences subjective discomfort. The likelihood of developing akathisia is highest in the first few weeks of treatment.

Serotonin syndrome, neuroleptic malignant syndrome

During treatment with paroxetine, serotonin syndrome or neuroleptic malignant syndrome-like symptoms can rarely develop, in particular if paroxetine is used in combination with other serotonergic drugs and / or antipsychotics. These syndromes can be potentially life-threatening and therefore treatment with paroxetine should be discontinued if they occur (the conditions are characterized by clusters of symptoms such as pyrexia, muscle rigidity, myoclonus, autonomic disturbances with possible rapid changes in vital signs, changes in mental status, including confusion consciousness, irritability, extremely severe agitation progressing to delirium and coma) and start supportive symptomatic therapy. Paroxetine should not be used in combination with serotonin precursors (such as L-tryptophan, oxytriptan) due to the risk of serotonergic syndrome.

Mania and Bipolar Disorder

A major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although not proven by controlled clinical trials) that treating such an episode with an antidepressant alone may increase the likelihood of an accelerated mixed or manic episode in patients at risk for bipolar disorder. Before initiating antidepressant treatment, a thorough screening should be performed to assess the patient's risk of developing bipolar disorder; such screening should include a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not indicated for the treatment of a depressive episode within a bipolar disorder. As with other antidepressants, paroxetine should be used with caution in patients with a history of mania.

Tamoxifen

Some studies have shown that the efficacy of tamoxifen, which was assessed by the risk of breast cancer recurrence and mortality, may decrease when combined with paroxetine as a result of paroxetine's irreversible inhibition of the CYP2D6 isoenzyme. The risk may increase with long-term joint use. When using tamoxifen for the treatment or prevention of breast cancer, consideration should be given to the use of alternative antidepressants that do not have an inhibitory effect on the CYP2D6 isoenzyme or have this effect to a lesser extent.

bone fractures

In epidemiological studies assessing the risk of developing bone fractures, an association of bone fractures with the intake of certain antidepressants, including drugs of the SSRI group, was revealed. The risk was observed during the course of antidepressant treatment and was maximal at the beginning of the course of therapy. The possibility of bone fractures should be considered when using paroxetine.

Diabetes

In diabetic patients, treatment with SSRIs may affect glycemic control. Doses of insulin and/or oral hypoglycemic agents may need to be adjusted.

MAO inhibitors

Treatment with paroxetine should be initiated with caution 2 weeks after discontinuation of treatment with irreversible MAOIs or 24 hours after discontinuation of treatment with reversible MAOIs. The dose of paroxetine should be increased gradually until the optimal therapeutic effect is achieved.

Impaired kidney or liver function

Epilepsy

As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.

Seizures

The frequency of seizures in patients taking paroxetine is less than 0.1%. If a seizure occurs, treatment with paroxetine should be discontinued.

Electroconvulsive therapy

There is only limited experience with the concomitant use of paroxetine and electroconvulsive therapy.

Glaucoma

As with other SSRIs, paroxetine can cause mydriasis and should be used with caution in patients with angle-closure glaucoma.

Hyponatremia

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

Bleeding

Bleeding through the skin and mucous membranes (including gastrointestinal and gynecological bleeding) has been reported in patients treated with paroxetine. Therefore, paroxetine should be used with caution in patients who are simultaneously receiving drugs that increase the risk of bleeding, in patients with a known bleeding tendency and in patients with diseases that predispose to bleeding.

Heart disease

When treating patients with heart disease, the usual precautions should be observed.

Symptoms observed upon discontinuation of paroxetine treatment in adults

According to the results of clinical studies in adults, the incidence of adverse reactions upon discontinuation of treatment in patients taking paroxetine was 30%, while the incidence of adverse reactions in the placebo group was 20%.

The occurrence of withdrawal symptoms does not mean that the drug is habit-forming or addictive, as is the case with substances of abuse.

Withdrawal symptoms have been described such as dizziness, sensory disturbances (including paresthesias, electric shock and tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, tremors, confusion, increased sweating, headache and diarrhea, palpitations, emotional lability, irritability, and visual disturbances. Usually these symptoms are mild or moderate, but in some patients they can be severe. Usually, symptoms develop in the first few days after discontinuation of the drug, but in very rare cases they occur in patients who accidentally missed a dose. As a rule, these symptoms resolve spontaneously and disappear within 2 weeks, but in some patients the symptoms may persist for much longer (2-3 months or more). It is recommended to reduce the dose of paroxetine gradually, over several weeks or months before completely canceling it, depending on the needs of the individual patient.

Symptoms observed upon discontinuation of paroxetine treatment in children and adolescents

Based on the results of clinical studies in children and adolescents, the incidence of adverse reactions upon discontinuation of treatment in patients taking paroxetine was 32%, while the incidence of adverse reactions in the placebo group was 24%. After the withdrawal of paroxetine, the following adverse reactions were recorded in at least 2% of patients and occurred at least 2 times more often than in the placebo group: emotional lability (including suicidal thoughts, suicidal attempts, mood changes and tearfulness), nervousness, dizziness , nausea and abdominal pain.

Despite the fact that paroxetine does not increase the negative effect of alcohol on psychomotor functions, it is not recommended to use paroxetine and alcohol at the same time.

Influence on the ability to drive vehicles and control mechanisms

Clinical experience with the use of paroxetine indicates that it does not impair cognitive and psychomotor functions. However, as in the treatment of any other psychotropic drugs, patients should be especially careful when driving a car and working with mechanisms.

Pregnancy and lactation

Fertility

Animal studies have shown that paroxetine may affect the quality of semen. Data from in vitro human studies may indicate some effect on semen quality, but human case reports of certain SSRIs (including paroxetine) have shown reversible effects on semen quality.

To date, no effect on human fertility has been observed.

Pregnancy

Animal studies have not revealed teratogenic or selective embryotoxic activity in paroxetine.

Epidemiological studies of pregnancy outcomes when taking antidepressants in the first trimester have revealed an increased risk of congenital anomalies, in particular of the cardiovascular system (eg, ventricular and atrial septal defects), associated with the use of paroxetine. According to available data, the incidence of defects in the cardiovascular system with the use of paroxetine during pregnancy is approximately 1/50, while the expected occurrence of such defects in the general population is approximately 1/100 newborns.

When prescribing paroxetine, the physician should consider alternative treatment in pregnant women and women planning pregnancy. Paroxetine should only be used if the potential benefit outweighs the potential risk. If a decision is made to discontinue treatment with paroxetine during pregnancy, the physician should follow the recommendations in the "Dosage regimen" and "Special instructions" sections.

There have been reports of preterm birth in women who received paroxetine or other SSRIs during pregnancy, although a causal relationship between taking these drugs and preterm birth has not been established.

It is necessary to carefully monitor the health of those newborns whose mothers took paroxetine in late pregnancy, since there are reports of complications in newborns associated with the use of paroxetine or other drugs of the SSRI group in the third trimester of pregnancy. However, a causal relationship between these complications and this drug therapy has not been confirmed. The clinical complications described included: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, arterial hypertension, arterial hypotension, hyperreflexia, tremor, neuroreflex hyperexcitability syndrome, irritability, lethargy, constant crying and sleepiness. In some reports, the symptoms have been described as neonatal manifestations of the withdrawal syndrome. In most cases, the described complications occurred immediately after childbirth or shortly after them (<24 ч).

According to epidemiological studies, the use of SSRI drugs (including paroxetine) during pregnancy, especially in the later stages, is associated with an increased risk of developing persistent pulmonary hypertension in newborns. An increased risk is observed in children born to mothers who took SSRI drugs in late pregnancy, 4-5 times higher than observed in the general population (1-2 per 1000 pregnancies). The results of animal studies have shown reproductive toxicity of the drug, but no direct adverse effects on pregnancy, embryonic and fetal development, childbirth or postnatal development have been shown.

breastfeeding period

Small amounts of paroxetine pass into breast milk. In published studies in breastfed children, paroxetine levels were undetectable (<2 нг/мл) или очень низкой (<4 нг/мл). У детей никаких признаков воздействия препарата выявлено не было. Тем не менее, пароксетин не следует принимать во время грудного вскармливания за исключением тех случаев, когда польза терапии для матери превышает потенциальный риск для ребенка.

In elderly patients, treatment should begin with the adult dose, which may then be increased to 40 mg/day.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life - 3 years. Do not use after the expiry date stated on the packaging.

Perhaps one of the most famous antidepressants of the group of selective serotonin reuptake inhibitors is Paxil. It is he who is preferred by many, because he is able to deal with both stressful and anxiety states, that is, he copes with all widespread as well as panic attacks or social phobias.

More about the release form

In the modern market of medicines "Paxil", patient reviews - confirmation of this, can only be found in the form of tablets that are intended for internal use. In appearance, these are ordinary round, white, coated pills, slightly convex on both sides. The variety of the assortment is only in the fact that there are packages of 10, 30 or one hundred pieces.

We study the composition

Regardless of the package with how many tablets you choose, each pill will contain 20 mg of the active ingredient - paroxetine. Not without such auxiliary components as calcium hydrophosphate dihydrate, magnesium stearate, and others.

How does Paxil work for a person suffering from depression or panic attacks?

As already mentioned, doctors confirm this, it is able to selectively (that is, selectively) block the uptake of serotonin, and the result of such an action is an antidepressant or anti-anxiety effect. That is why this drug is used only in this area.

"Paxil", reviews of doctors about this can often be found, this is for people who are depressed and who are being persecuted. As practice shows, this drug will cope, even if other medications that were previously taken by the patient were powerless. By the way, it is also recommended to take it for the prevention of relapses of depression.

But if a person suffers from panic conditions, Paxil (instructions for use, reviews and recommendations of doctors confirm this) is best taken only in combination with nootropic drugs or tranquilizers that the attending physician will prescribe.

Why is Paxil prescribed to many? Because this is the drug that will not affect a person like a sleeping pill, while it does not worsen the quality of sleep, that is, no additional funds will have to be used to get rid of such consequences. Although if the patient has had problems with sleep, the attending physician may decide on the need to take such drugs in combination.

"Paxil", reviews of doctors also say about this, does not affect the activity of the brain, which is very important, that is, its work is not inhibited. There will be no drop in blood pressure or change in heart rate while taking this drug.

How quickly can you notice the results of the drug?

If we talk about a really significant, clearly visible effect from the use, then it can be observed already in the second week of taking the medication. And if we talk about persistent action, then practitioners see it in their patients after two full weeks of taking it.

Consider in detail the indications for use

We have already figured out that Paxil is necessary for problems in the mental sphere. To be more precise, it is prescribed for the following symptoms and diseases:

• depression. Moreover, depression of any type, including those accompanied by anxiety.
• Obsessive-compulsive disorders. These are conditions in which a person has an irresistible desire to fight the problems that may appear.
• type. Paxil, patient reviews confirm, helps even with such disorders, which are accompanied by a fear of open spaces.
• Social phobia. Today, many people attribute social phobia to themselves, perceiving it simply as a little nervousness from the realization that they will need to speak in public. Real social phobia is much more serious and brings a lot of worries and problems to the patient, which is why Paxil can be prescribed with such a diagnosis.
• If a patient is diagnosed with a daily anxiety condition or even a generalized anxiety disorder, he may also be prescribed the drug described.
• If a person has had depression before or has experienced a severe form of stress, Paxil antidepressants can also be attributed to him, reviews of the treatment with this particular remedy are in most cases positive.

Of course, such a drug may not act as the main element of treatment, but as, for example, supportive. With post-traumatic stress, it will always be taken only for the purpose of treatment.

Let's talk about the correct application

Since the average dose of the drug for 24 hours is 20 mg, it is often prescribed to take only one tablet per day. It is important to know that the tablet must be swallowed whole, without crushing it before taking it and in no case chewing it.

"Paxil", instructions for use, reviews of practitioners warn about this, you need to take it until all the symptoms of the disease are stopped. Often, the course of treatment lasts more than one month, in each individual case it is worth listening only to the recommendations of the treating specialist, who will monitor the recovery process and make a timely decision to stop the course of therapy.

With depression

So, for depression, Paxil, according to the recommendations of doctors, is used one tablet per day for at least two to three weeks, after which it will be possible to begin to evaluate the results of such treatment. If the doctor considers the improvements not significant enough, he may increase the daily dosage of the drug. The maximum dosage is 50 mg per day. You should know that the dosage increases very smoothly - only 10 mg per week and under the constant supervision of the attending specialist. If, after the first increase in dosage, the drug was taken for more than seven days and the improvements are imperceptible or hardly noticeable, a second increase in dosage is possible. It is important to regularly evaluate the effectiveness of Paxil in order to stop treatment in time until the patient becomes addicted to the drug.

The average course of treatment can last from 4 to 12 months, as already mentioned, for each individual case, a different course of treatment is selected. After this, the gradual withdrawal of the drug begins.

For panic disorder

The fact that Paxil is very effective in panic disorders is confirmed by doctors' reviews. With such diseases, the average dosage rate is 40 mg per day. The maximum may be 60 mg for 24 hours. As with depression, an increase in dosage can be started after two to three weeks of use, which did not bring a significant result, and only 10 mg per week. For children, the dosage is much less for such diseases, it will be from 20 to 30 mg per day. The maximum allowed children to prescribe 50 mg per day. The drug begins with 10 mg per day and the dosage is also increased once a week by 10 mg.

With such diseases, the course of treatment lasts an average of 4-8 months. After the gradual withdrawal of the drug begins.

The right way to deal with social phobia

Symptoms of social phobia are perfectly relieved at 20 mg per day for adults and 10 mg per day for children and adolescents. In such cases, they begin to take the medicine "Paxil" (reviews of doctors and the patients themselves confirm this) with 10 mg, after which the dosage is increased by 10 mg once a week. Once the doctor confirms that the dosage is sufficient for treatment, it will not be further increased until the very end of the course of treatment. The average course lasts 4 months, although there have been many cases where 10 months were needed.

Anxiety disorders and Paxil

Instructions, reviews of doctors note that for most patients, 8 months of treatment is enough to finally overcome generalized anxiety disorder. Often, a dosage of 20 mg is enough for 24 hours, although if necessary it can be increased to 50 mg (the dosage is still increased by 10 mg per week, no more).

Stress disorders, including post-traumatic

One tablet per day with this disease is enough for most patients. The maximum dosage in such cases is allowed in the amount of 50 mg, you can increase it to 10 mg once a week. With such problems, Paxil tablets, medical reviews about this can often be found, help in 4-7 months.

Proper Cancellation

The reviews of those addicted to Paxil confirm that if you do not follow the rules described below, you can seriously harm your health. So, "Paxil" is the drug that requires a slow and gradual withdrawal. Schematic algorithm of actions:

• the size of the last dosage is reduced by 10 mg and for another week we take the drug according to the new dosage;
• every week you need to reduce the dosage by half a tablet or 10 mg until you reach a dosage of 20 mg, it is in this amount that you need to take the drug for another week, and after that completely abandon it.

What should you do if you or your healthcare provider notice a deterioration from stopping Paxil? Reviews of the best modern experts in this case recommend resuming the previous dosage of the drug, drinking it in this amount for another 2 or 3 weeks, and then start the cancellation process again. If necessary, reduce the dosage of the drug by half a tablet or 10 mg once every three weeks, the main thing is that the withdrawal of the drug does not harm the improved health of the patient.

Can pregnant or lactating mothers take the drug?

Animal experiments have not shown any changes or negative effects from the use of this drug by pregnant or lactating women, no changes were observed in either the female or the fetus.

But clinical observations confirm that taking such a drug is dangerous in the first trimester of pregnancy, as it increases the risk of congenital anomalies and heart defects.

If mothers took Paxil in the third trimester, side effects (reviews of doctors confirm this) were expressed in the form of unstable temperature, problems with feeding the baby, increased reflexes, etc. Such complications occurred 5 times more often in mothers who took this drug than in mothers who did not take it.

If we talk about men, studies have shown that Paxil can also lower the quality of sperm, so when using this drug for treatment, conceiving a child should be postponed. Changes in sperm will reverse some time after the drug is completely discontinued, it is then that it is already worth starting to plan a pregnancy.

Does Paxil affect the ability to drive or use machines?

As observations of patients who are treated with this particular drug show, no changes, deterioration in the ability to drive a car or operate machinery are observed. But still, a person should listen to himself, and if there is a feeling of deterioration, it is worth refusing to perform such actions.

What do doctors say about an overdose?

As shown by previous experiments, side effects from this drug can be observed only if 100 tablets are taken at the same time. An overdose will be expressed in the form of a significant dilation of the pupils, severe vomiting and an increase in the level of anxiety. In this case, you should immediately wash the patient's stomach and leave it under the supervision of specialists.

Death from "Paxil" was observed only in the case of its combination with those who could not interact with it. "Paxil" and alcohol, reviews confirm, it is also a deadly cocktail if the dosage of the first and second components is not observed. In addition, it should be understood that even if you drink quite a bit of alcohol, if you are taking this drug, such an action will reduce the effectiveness of the treatment to zero. It is also possible that the side effects of taking this drug will increase if you regularly drink alcohol, albeit in small quantities.

What is often observed during cancellation?

Sometimes patients develop a "withdrawal syndrome", with Paxil this is also possible. So, with the withdrawal syndrome, it is from this medication that the following can be observed:

• feeling of dizziness;
• minor sleep disturbance
• brief periods of confusion;
• regular nausea that cannot be removed with proper nutrition or special preparations;
• sweating of the palms or the body as a whole;
• sometimes (very rarely) diarrhea is observed.

Often, some of the above symptoms are observed only in the first days of drug withdrawal, as this is really a small stress for the body, for which it was not ready. Also, similar consequences can be in people who missed taking the medicine (several pills in a row) or took alcohol. Experts say that the withdrawal syndrome will last a maximum of two weeks, and the patient does not need any specific treatment, you just have to survive this period in order to return to normal life without such medications. That is why it is worth canceling the described drug in stages.

Are there any contraindications?

"Paxil" is not prescribed to children under 18 years of age for the treatment of depressive conditions. It is also not recommended for children who have not yet reached the age of seven. Before use, you should carefully read the list of excipients to make sure that you do not have an individual hypersensitivity to them.

And a couple of words about the drug

"Paxil" deserved positive reviews from the majority of patients who took it. According to experts, this drug can only receive negative reviews if it is. If the person himself or his doctor did not follow the instructions for use. If you take these pills without a doctor's prescription, you can seriously harm your health or become addicted to antidepressants. Experts recommend combining taking this drug with regular visits to a psychologist and strict adherence to instructions and recommendations. In order for the treatment process to really give results, it is better to completely abandon the intake of alcohol, even in small doses.

Antidepressant, selective serotonin reuptake inhibitor. It has a bicyclic structure, different from the structure of other known antidepressants.

It has an antidepressant and anxiolytic effect with a fairly pronounced stimulating (activating) effect.

The antidepressant (thymoanaleptic) effect is associated with the ability of paroxetine to selectively block the reuptake of serotonin by the presynaptic membrane, which causes an increase in the free content of this neurotransmitter in the synaptic cleft and an increase in its activity in the central nervous system.

The effect on m-cholinergic receptors, α- and β-adrenergic receptors is insignificant, which determines the extremely weak severity of the corresponding side effects.

Pharmacokinetics

After oral administration, paroxetine is well absorbed from the gastrointestinal tract. Eating does not affect absorption. C ss is established by 7-14 days from the start of therapy.

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

T 1 / 2 averages 16-24 hours. Less than 2% is excreted in the urine unchanged, the rest - in the form of metabolites either in the urine (64%) or in the bile.

Excretion of paroxetine is biphasic.

With long-term continuous administration, pharmacokinetic parameters do not change.

Release form

White, oval, biconvex, film-coated tablets, debossed with "20" on one side and a notch on the other.

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

The composition of the film shell: white opadry - 7 mg (hypromellose - 4.2 mg, titanium dioxide - 2.2 mg, macrogol 400 - 0.6 mg, polysorbate 80 - 0.1 mg).

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

Dosage

When taken orally, the initial dose is 10-20 mg / day. If necessary, depending on the indications, the dose is increased to 40-60 mg / day. The dose increase is carried out gradually - by 10 mg with an interval of 1 week. Reception frequency - 1 time / day. The treatment is long. The effectiveness of therapy is assessed after 6-8 weeks.

For elderly and debilitated patients, as well as for impaired renal and hepatic function, the initial dose is 10 mg / day; the maximum dose is 40 mg / day.

Interaction

With simultaneous use with paroxetine, it is possible to increase plasma concentrations of drugs metabolized with the participation of the CYP2D6 isoenzyme of the cytochrome P 450 system (antidepressants, antipsychotics, phenothiazine derivatives, class IC antiarrhythmic drugs).

With the simultaneous use of agents that induce or inhibit protein metabolism, changes in the metabolism and pharmacokinetic parameters of paroxetine are possible.

With simultaneous use, the effect of alprazolam is enhanced due to a decrease in its metabolism due to inhibition of CYP3A isoenzymes of the cytochrome P450 system under the influence of paroxetine.

With simultaneous use with warfarin, oral anticoagulants, an increase in bleeding time is possible with unchanged prothrombin time.

With simultaneous use with dextromethorphan, dihydroergotamine, cases of serotonin syndrome are described.

With simultaneous use with interferon, a change in the antidepressant effect of paroxetine is possible.

The simultaneous use of tryptophan can cause the development of serotonin syndrome, manifested by agitation, anxiety, disorders of the gastrointestinal tract, including diarrhea.

With simultaneous use with perphenazine, it increases the side effects from the central nervous system due to inhibition of the metabolism of perphenazine under the influence of paroxetine.

With simultaneous use, the concentration in the blood plasma of tricyclic antidepressants increases, there is a risk of developing serotonin syndrome.

Simultaneous administration of cimetidine increases the concentration of paroxetine in the blood plasma.

Side effects

From the side of the central nervous system: rarely (when used in doses of more than 20 mg / day) - drowsiness, tremor, asthenia, insomnia.

From the digestive system: rarely (when used in doses of more than 20 mg / day) - nausea, dry mouth; in some cases - constipation.

Others: rarely (when used in doses of more than 20 mg / day) - increased sweating, ejaculation disorders.

Indications

Endogenous, neurotic and reactive depressions.

Contraindications

Simultaneous use of MAO inhibitors and a period of up to 14 days after their withdrawal, increased sensitivity to paroxetine.

Application features

Application for violations of liver function

Application for violations of kidney function

Use in elderly patients

special instructions

Stopping the use of paroxetine should be carried out by gradually reducing the dose, in order to avoid the withdrawal syndrome, which is manifested by dizziness, nausea, vomiting, insomnia, confusion, increased sweating.

During treatment with paroxetine, alcohol is contraindicated.

Use with caution 14 days after the abolition of MAO inhibitors, gradually increasing the dose. MAO inhibitors should not be prescribed within 2 weeks after the complete withdrawal of paroxetine.

When used simultaneously with drugs that inhibit the metabolism of liver enzymes, paroxetine should be used at the lowest recommended doses. When used simultaneously with drugs that induce enzyme metabolism, no change in the initial doses of paroxetine is required.

Use paroxetine with caution with lithium preparations (it is recommended to control the concentration of lithium in the blood plasma), oral anticoagulants.

In experimental studies, the carcinogenic and mutagenic properties of paroxetine have not been established.

Influence on the ability to drive vehicles and control mechanisms

Use with caution in patients whose activities are associated with the need for a high concentration of attention and speed of psychomotor reactions.

; SSRIs
Pharmacological action: Paxil is a potent and selective 5-hydroxytryptamine (5-HT, serotonin) reuptake inhibitor. It is generally accepted that its antidepressant activity and effectiveness in the treatment of obsessive-compulsive disorder (OCD) and panic disorder are due to the specific inhibition of serotonin reuptake in brain neurons.
Effects on receptors: Muscarinic cholinergic receptors (weak affinity); Alpha1-, alpha2- and beta-adrenergic receptors (weak affinity) Dopamine (D2), 5-HT1-like, 5HT2- and histamine (H1) receptors (weak affinity).
Systematic (IUPAC) name: (3S, 4R) -3 - [(2H-1,3-benzodioxol-5-yloxy) methyl] - 4 - (4-fluorophenyl) piperidine
Trade names: Paxil, Pexeva, Brisdelle
Legal Status: Available by prescription only
Application: oral
Bioavailability: completely absorbed from the gastrointestinal tract, initially metabolized in the liver; the time to reach the maximum concentration of the drug is from 4.9 hours (with food) to 6.4 hours (on an empty stomach).
Plasma protein binding: 93-95%
Metabolism: extensive, hepatic (mainly mediated by CYP2D6)
Half-life: 24 hours (range 3-65 hours)
Excretion: 64% in urine, 36% in bile
Formula: C19H20FNO3
Mol. weight: 329.3

Paxil (also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin, and Brisdelle) is an SSRI (Selective Serotonin Reuptake Inhibitor) type of antidepressant. Paxil is used to treat major depressive episodes, obsessive-compulsive disorder, panic disorder, social anxiety, post-traumatic stress disorder, generalized anxiety disorder, and vasomotor symptoms (eg, hot flashes and night sweats) associated in adult menopausal outpatients. In 1992, the drug was introduced to the market by the pharmaceutical company SmithKline Beecham (now GlaxoSmithKline). Since 2003, since the expiration of the patent, generics of the drug begin to appear. In adults, the effectiveness of Paxil for the treatment of depression is comparable to previous generations of tricyclic antidepressants, with fewer side effects and less toxicity. The differences with the newer antidepressants are more subtle and mostly limited to side effects. The drug has common side effects and contraindications with other SSRIs, including nausea, drowsiness and sexual side effects. Paxil causes clinically significant weight gain. Trials of Paxil in cases of childhood depression failed to demonstrate that it has a greater statistical effect than placebo. Stopping Paxil is associated with a high risk of withdrawal. Due to the increased risk of birth defects, pregnant women and women planning pregnancy are advised to consult their doctor before using the drug.

Medical use

Paxil is primarily used to treat symptoms of depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, generalized anxiety disorder (GAD), social phobia/social anxiety disorder, and premenstrual dysphoric disorder (PMDD). Paxil is the first antidepressant approved in the US for the treatment of panic attacks.

Research

Paxil is a widely used antidepressant in a class of drugs known as selective serotonin reuptake inhibitors, or SSRIs. Several studies have shown that Paxil can be used to treat premature ejaculation. In particular, the drug increases the intravaginal latent ejaculation time by 6-13 times, which is more than other SSRIs (Fluvoxamine, and). However, an "emergency" dose of Paxil ("on demand") 3-10 hours before intercourse only results in a "clinically inappropriate and sexually unsatisfactory" delay in ejaculation by 1.5 times. The drug is inferior to clomipramine, which causes a four times longer delay. The reason the drug causes delayed ejaculation is that it significantly reduces sexual desire and in some cases even causes an inability to achieve an erection or ejaculate. SSRIs are also effective for treating severe premenstrual syndrome; however, due to its teratogenic effects and high risk of withdrawal in adults and neonates, Paxil is contraindicated in women who may become pregnant. There is also evidence that Paxil may be effective in treating gambling and hot flashes. The possible benefits of Paxil for the treatment of diabetic neuropathy or chronic headache are still unclear. New evidence suggests that antipsychotics may be used as an adjunct or alternative to Paxil in patients with generalized anxiety disorder. Although the available evidence is rather conflicting, Paxil may be an effective treatment for dysthymia, a chronic illness with depressive symptoms.

The effectiveness of Paxil

According to the package leaflet provided by Paxil's manufacturer of Paxil (GlaxoSmithKline) and approved by the US FDA, Paxil's efficacy in major depressive disorder has been proven in six placebo-controlled clinical trials. In adults, the effectiveness of Paxil in the treatment of depression is comparable to that of previous generation tricyclic antidepressants. Randomized trials have shown that Paxil is more effective than placebo for the treatment of depression in elderly patients. Three 10- to 12-week studies have demonstrated superiority of Paxil over placebo in the treatment of panic disorder. Three 12-week studies of adult outpatients demonstrated that patients with social anxiety disorder responded better to Paxil than to placebo.

Paxil Side Effects

Sexual dysfunction is a common side effect of SSRIs. In particular, side effects often include difficulty becoming aroused, lack of interest in sex, and anorgasmia (trouble reaching orgasm). Genital anesthesia, loss or decreased response to sexual stimuli, and ejaculatory anhedonia are also possible. Although these sexual side effects are usually reversible, they may last for months or years after the drug is completely stopped. This feature has been called "post-SSRI sexual dysfunction." Among the common side effects of Paxil associated with the treatment of depression and listed in the annotation to the drug, the effects with the greatest difference from placebo are: nausea (26% Paxil vs 9% in the placebo group), drowsiness (23% vs 9% in the placebo group), ejaculatory disorders (13% vs 0% placebo), other male sexual disorders (10% vs 0% placebo), asthenia (15% vs 6% placebo), sweating (11% vs 2% placebo) , dizziness (13% vs 6% placebo), insomnia (13% vs 6% placebo), dry mouth (18% vs 12% placebo), constipation (14% vs 9% placebo) and tremor (8% versus 2% in the placebo group). Other side effects include high blood pressure, headache, agitation, weight gain, memory impairment, paresthesia, and reduced fertility. Common side effects are observed mainly during the first 1-4 weeks while the body becomes tolerant to the drug, and once this happens, discontinuation of the drug can cause the opposite effect with symptoms reappearing in an increased form for a very long time. Almost all SSRIs are known to cause one or more of these symptoms. A person taking Paxil may experience several of the listed side effects, all or none of them. Most side effects disappear or decrease with continued treatment, although some of them may last throughout the duration of treatment. Side effects are also often dose dependent. Fewer and/or less severe symptoms are observed at lower doses and/or more severe symptoms are observed at higher doses. Increases or changes in dosage may also cause a recurrence or worsening of symptoms. On December 9, 2004, the EMA Committee on Medicinal Products for Human Use informed patients, counselors and parents that Paxil should not be given to children. The committee also advised prescribers to closely monitor adult patients at high risk for suicidal behavior and/or suicidal ideation. The Committee does not prohibit the use of Paxil in high-risk adults, but calls for extreme caution in its use. Due to reports of adverse reactions after discontinuation of treatment, a gradual dose reduction over several weeks or months is recommended. Cases of akathisia and suicidal behavior have been observed while taking Paxil. As stated in the Paxil product information in the UK, alcohol abuse may also occur while taking the drug. Rarely, a severe side effect, serotonin syndrome, can occur. Most patients, both men and women, have sexual side effects when taking Paxil and other SSRIs. In men, Paxil may also be associated with sperm DNA fragmentation. A serious side effect of Paxil can be mania or hypomania, which affects up to 8% of psychiatric patients. This side effect can occur in people without a history of mania and is most commonly seen in patients with bipolar disorder or hereditary factors. Schmitt et al. (2001) suggested that Paxil had a negative effect on long-term memory without affecting short-term memory, although these findings have not been independently verified. In a study of healthy participants who took Paxil for 14 days (20 mg for days 1-7 and 40 days 8-14 mg), there was a worsening of word recall on the 14th day, compared with the placebo group. Schmitt et al. did not take into account the significant difference at the outset of the study in the ability to recall words between the Paxil and placebo groups, however, this difference could be the reason for the significant difference in the groups at day 14. In addition, participants taking Paxil were able to recall the same number of words at baseline and on study day 14, which is not consistent with the finding that Paxil negatively affects word recall.

Contraindications

Paxil is contraindicated in all patients under 18 years of age, in patients taking any of the drugs listed in the interactions section below, and in adults who are pregnant or who may become pregnant. Paxil may also be contraindicated in many adult males due to the sexual and reproductive side effects described below. In the United States, the FDA requires a black box warning (the most serious type of warning on prescription drug labels) to be on the drug because of the increased risk of suicidal thoughts and behavior when taking the drug. The warning also applies to other SSRIs, but Paxil has been a concern since suicidal behavior began to be reported in trials. The Medicines and Medical Devices Regulatory Agency recommends that people under 18 years of age not use Paxil.

Suicide risk

Paxil may increase the risk of suicidal thoughts and behavior in children and adolescents. Due to the fact that real suicide when taking the drug comes quite rarely, it is difficult to assess the impact of Paxil on the risks of this kind. However, some studies analyze suicidal tendencies based on data on suicidal thoughts and suicidal behavior of the patient. In 2004, the FDA conducted a statistical analysis of clinical trials of Paxil in children and adolescents, which found an increase in rates of "suicidal behavior" and thoughts compared with placebo; a trend towards an increase in "suicidal behavior" has been observed in studies of both depression and anxiety disorders. A review of SSRIs by the University of North Carolina found that the average risk of suicide among adolescents was 4%, compared with 2% in the placebo group, and among all patients, "the highest risk of self-mutilation was observed among users of Paxil."

withdrawal syndrome

Many psychoactive drugs can cause withdrawal symptoms (withdrawal symptoms) when they are stopped. The data showed that Paxil has one of the highest withdrawal severity rates of any drug in its class. Common withdrawal symptoms upon discontinuation of Paxil include: nausea, dizziness and lightheadedness, insomnia, nightmares and vivid dreams, a feeling of electricity in the body, and a tendency to cry and worry. Taking Paxil in liquid form can provide a very gradual dose reduction, which may reduce the risk of withdrawal symptoms. A temporary switch to is also recommended, which has a longer half-life and therefore reduces the severity of the withdrawal syndrome. In addition, The Lancet published an analysis of World Health Organization data showing that taking SSRIs during pregnancy can cause withdrawal symptoms in newborns, including seizures. Among the "93 cases with suspected SSRI-induced neonatal withdrawal ... 64 were associated with Paxil, 14 with , nine with and seven with citalopram."

Paxil and pregnancy

The American College of Obstetricians and Gynecology recommends that pregnant women and women planning to become pregnant should "individualize treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy and avoid Paxil if possible." According to the annotation to the drug, “epidemiological studies have shown that children born to women who took Paxil in the first trimester of pregnancy had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSD and ASD). In general, septal defects are classified as symptomatic, which may require surgery, and asymptomatic, which may resolve without assistance. In the event of a sudden pregnancy in a patient taking Paxil, the attending physician should warn her of the potential harm to the fetus. If the benefit of Paxil to the mother does not justify continued treatment, consider discontinuing Paxil or switching to another antidepressant. For women planning to become pregnant or for women in the first trimester of pregnancy, Paxil should only be initiated after consideration of other available treatment options. These findings are supported by several systematic reviews and meta-analyses, showing that, on average, the use of Paxil during pregnancy is associated with an approximately 1.5-1.7-fold increase in birth defects, in particular heart defects. A recent non-systematic review by Salvatore Gentil in the Journal of Clinical Psychiatry, sponsored or funded by GSK (GlaxoSmithKline), concludes otherwise: "The teratogenic potential of Paxil reported in some studies remains unproven." Gentil talks about the need for large, epidemiological, prospective, controlled trials of "mothers who take Paxil during pregnancy." Other opinions about whether the teratogenic risk outweighs the risk of relapse when the drug is stopped are rather controversial. Some are in favor of discontinuation, while others speak of the need for caution; and even where the review of antidepressants is generally favorable, Paxil stands out as having specific risks. The use of Paxil during pregnancy increases the risk of spontaneous miscarriage. A large 2010 study using medical birth registration data in Sweden from July 1, 1995 to 2007 identified women who reported using antidepressants in early pregnancy or who were prescribed antidepressants during pregnancy as antenatal care, showed a specific association between Paxil use and childhood cardiovascular defects. This study also concluded that there was an association between Paxil and hypospadias, although the investigators concluded that it is still not clear whether these effects depend on the use of the drugs or on the underlying pathology. Abrupt discontinuation of psychotropic drugs during pregnancy can lead to serious adverse effects. The neonatal withdrawal symptoms of Paxil described above have been observed in mothers taking Paxil during pregnancy.

Interactions

GlaxoSmithKline warns that drug interactions may create or increase specific risks, including serotonin syndrome or neuroleptic malignant syndrome and similar reactions:

The development of potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome and similar reactions has been reported with SSRIs and SSRIs taken alone, including Paxil, and especially with the combined use of serotonergic drugs (including triptans) with drugs that impair serotonin metabolism (in including MAO inhibitors) or with antipsychotic or other dopamine antagonists.

The prescribing information states that Paxil “should not be used in combination with MAO inhibitors (including linezolid, an antibiotic that is a reversible non-selective MAO inhibitor) or within 14 days of stopping MAO use”, and should not be combined with pimozide, thioridazine , Tryptophan or . Paxil is metabolized by cytochrome P450 2D6. The drug Tamoxifen for the treatment of breast cancer is also metabolized into the active state by the same cytochrome. Patients taking Paxil and Tamoxifen have an increased risk of death from breast cancer (from 24% to 91%), depending on the duration of co-administration of the drugs.

Overdose

Acute overdose is often manifested by vomiting, lethargy, ataxia, tachycardia and convulsions. Plasma, serum or blood concentrations of Paxil may be measured to monitor a patient's condition, to confirm a diagnosis of poisoning in hospitalized patients, or to assist in a forensic examination of deceased patients. Plasma concentrations of Paxil are typically in the range of 40-400 µg/l in individuals receiving daily therapeutic doses of the drug and 200-2000 µg/l in poisoned patients. Postmortem levels of Paxil in the blood during acute overdose in fatal situations are 1-4 mg / l.

Pharmacology

Paxil is the most potent and one of the most specific serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs). Due to the effect of the drug on the neurons of the brain, it exhibits its antidepressant effect. The substance is structurally close to:

SERT - serotonin transporter (Ki = 0.04 nm) NET - norepinephrine transporter (Ki = 90 nm) DAT - dopamine transporter (Ki = 400 nm)

Paxil is a phenylpiperidine derivative not chemically related to tricyclic or tetracyclic antidepressants. In receptor binding studies, Paxil did not show significant affinity for adrenergic (alpha1, alpha2, beta), dopaminergic, serotonergic (5HT1, 5HT2) or histamine receptors in rat brain membranes. There was a weak affinity of the drug for muscarinic acetylcholine and norepinephrine receptors. Paxil's predominant metabolites account for approximately 1/50th of Paxil's potency and are essentially inactive. Paxil has been shown to have antimicrobial activity against several groups of microorganisms, mainly Gram-positive microorganisms. In combination with certain antibiotics, the drug also acts synergistically against a number of bacteria. In addition, Paxil demonstrates antifungal activity, being the most potent drug against Candida Albicans DSY1204 hypersusceptible strains.

Formulas

Paxil CR (controlled release) is associated with a reduction in nausea during the first week of treatment compared with immediate release Paxil. However, the dependence of treatment discontinuation due to nausea was not significantly different between the drugs.

Dispute

Implementation

In 2007, Paxil ranked 94th on the best-selling drug list with sales of over $1 billion. In 2006, Paxil was the fifth most commonly prescribed antidepressant in the US retail market, with over 19.7 million prescriptions. Sales dropped to 18.1 million in 2007, but Paxil is still the fifth most commonly prescribed antidepressant in the US.

Ingredients: Paxil

The active substance of the drug: paroxetine
ATX encoding: N06AB05
CFG: Antidepressant
Reg. number: P No. 016238/01
Date of registration: 27.05.05
The owner of the reg. Award: GLAXO WELLCOME PRODUCTION (France)

White, film-coated, oval, biconvex tablets, debossed with "20" on one side and a break line on the other.
1 tab.
paroxetine hydrochloride hemihydrate
22.8 mg
which corresponds to the content of paroxetine
20 mg

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

Shell composition: hypromellose, titanium dioxide, macrogol 400, polysorbate 80.

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

The description of the drug is based on the officially approved instructions for use.

Pharmacological action Paxil

Antidepressant. It belongs to the group of selective serotonin reuptake inhibitors.

The mechanism of action of Paxil is based on its ability to selectively block the reuptake of serotonin (5-hydroxytryptamine /5-HT/) by the presynaptic membrane, which is associated with an increase in the free content of this neurotransmitter in the synaptic cleft and an increase in serotonergic action in the central nervous system responsible for the development of thymoanaleptic (antidepressive) effect.

Paroxetine has a low affinity for m-cholinergic receptors (has a weak anticholinergic effect), 1-, 2- and -adrenergic receptors, as well as dopamine (D2), 5-HT1-like, 5-HT2-like and histamine H1 receptors.

Behavioral and EEG studies show that paroxetine exhibits weak activating properties when given at doses above those needed to inhibit serotonin uptake. Paroxetine does not affect the cardiovascular system, does not disrupt psychomotor functions, and does not depress the central nervous system. 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 psychotropic activity profile of Paxil are antidepressant and anti-anxiety effects. Paroxetine may cause mild activating effects at doses in excess of those required to inhibit serotonin reuptake.

In the treatment of depressive disorders, paroxetine has shown efficacy comparable to that of tricyclic antidepressants. Paroxetine is therapeutically effective even in patients who have not responded adequately to prior standard therapy. Patients' condition improves as early as 1 week after the start of treatment, but outperforms placebo only at 2 weeks. Taking paroxetine in the morning does not adversely affect the quality and duration of sleep. Moreover, with effective therapy, sleep should improve. During the first few weeks of taking paroxetine, patients with depression and suicidal thoughts improve.

The results of studies in which patients took paroxetine for 1 year showed that the drug effectively prevents relapses of depression.

In panic disorder, the use of Paxil in combination with drugs that improve cognitive function and behavior turned out to be more effective than monotherapy with drugs that improve cognitive-behavioral function, which is aimed at correcting them.

Pharmacokinetics of the drug.

Suction

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

Distribution

Css is established by 7-14 days from the start of therapy. The clinical effects of paroxetine (side effects and efficacy) do not correlate with its plasma concentration.

Paroxetine is extensively distributed in tissues, and pharmacokinetic calculations show that only 1% of it is present in plasma, and at therapeutic concentrations, 95% is in protein-bound form.

Paroxetine has been found to be excreted in small amounts in breast milk and also crosses 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 efficacy of the drug is unlikely.

Since the metabolism of paroxetine involves a first pass through the liver, the amount detected in the systemic circulation is less than that absorbed from the gastrointestinal tract. With an increase in the dose of paroxetine or with repeated dosing, when the load on the body increases, there is a partial absorption of the "first pass" effect through the liver and a decrease in the plasma clearance of paroxetine. As a result, an increase in the concentration of paroxetine in plasma and fluctuations in pharmacokinetic parameters are possible, which can only be observed in those patients in whom low plasma levels of the drug are achieved when taking low doses.

breeding

It is excreted in the urine (unchanged - less than 2% of the dose and in the form of metabolites - 64%) or in the bile (unchanged - 1%, in the form of metabolites - 36%).

T1 / 2 varies, but averages 16-24 hours.

Excretion of paroxetine is biphasic, including primary metabolism (first phase) followed by systemic elimination.

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

Pharmacokinetics of the drug.

in special clinical situations

In elderly patients, as well as in severely impaired liver and kidney function, the plasma concentration of paroxetine is increased, and the range of plasma concentrations in them almost coincides with the range of healthy adult volunteers.

Indications for use:

Depression of all types, including reactive depression, severe endogenous depression and depression accompanied by anxiety (the results of studies in which patients received the drug for 1 year show that it is effective in preventing relapses of depression);

Treatment (including maintenance and preventive therapy) of obsessive-compulsive disorder (OCD) in adults, as well as in children and adolescents aged 7-17 years (it has been proven that the drug has been effective in the treatment of OCD for at least 1 year and in the prevention of relapses of OCD);

Treatment (including maintenance and prophylactic therapy) of panic disorder with and without agoraphobia (the effectiveness of the drug is maintained for 1 year, preventing relapses of panic disorder);

Treatment (including maintenance and preventive therapy) of social phobia in adults, as well as in children and adolescents aged 8-17 years (the effectiveness of the drug is maintained with long-term treatment of this disorder);

Treatment (including maintenance and preventive therapy) of generalized anxiety disorder (the effectiveness of the drug is maintained during long-term treatment of this disorder, preventing relapse of this disorder);

Treatment of post-traumatic stress disorder.

Dosage and method of application of the drug.

For adults with depression, the average therapeutic dose is 20 mg / day. With insufficient effectiveness, the dose may be increased to a maximum of 50 mg / day. The dose increase should be carried out gradually - by 10 mg with an interval of 1 week. The dose of Paxil should be reviewed and, if necessary, changed within 2-3 weeks from the start of therapy and thereafter until an adequate clinical effect is obtained.

For adults with obsessive-compulsive disorder, the average therapeutic dose is 40 mg / day. Start treatment with 20 mg / day, then gradually increase the dose by 10 mg every week. With insufficient clinical effect, the dose may be increased to 60 mg / day. For children aged 7-17 years, the drug is prescribed at an initial dose of 10 mg / day, gradually increasing by 10 mg every week. If necessary, the dose can be increased to 50 mg / day.

For adults with panic disorder, the average therapeutic dose is 40 mg / day. Treatment should begin with the use of the drug at a dose of 10 mg / day. The drug is used at 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 effectiveness, the dose may be increased to 60 mg / day.

For adults with social phobia, the average therapeutic dose is 20 mg / day. With insufficient clinical effect, the dose can be increased gradually by 10 mg weekly to 50 mg / day. For children aged 8-17 years, the drug is prescribed at an initial dose of 10 mg / day, gradually increasing by 10 mg every week. If necessary, the dose can be increased to 50 mg / day.

For adults with generalized anxiety disorder, the average therapeutic dose is 20 mg / day. With insufficient clinical effect, the dose can be increased gradually by 10 mg weekly to a maximum dose of 50 mg / day.

For adults with post-traumatic stress disorder, the average therapeutic dose is 20 mg / day. With insufficient clinical effect, the dose can be increased gradually by 10 mg weekly to a maximum of 50 mg / day.

In elderly patients, treatment should begin with the adult dose, which may then be increased to 40 mg/day.

In patients with severe impaired liver and kidney function (CC less than 30 ml / min), the dose of the drug should be reduced to the lower limit of the dose range.

The course of treatment should be long enough. Patients with depression or OCD should be treated for a period of time long enough for all symptoms to resolve. This period can take several months for depression, and even longer for OCD and panic disorder.

Paxil is taken 1 time / day in the morning with food. The tablet should be swallowed whole, without chewing, with water.

Cancellation of the drug

Abrupt discontinuation of the drug should be avoided. The daily dose should be reduced by 10 mg weekly. After reaching a daily dose of 20 mg in adults or 10 mg in children and adolescents, patients continue to take this dose for a week and then the drug is completely canceled.

If withdrawal symptoms develop during dose reduction or after discontinuation of the drug, it is advisable to resume taking the previously prescribed dose. Subsequently, you should continue to reduce the dose of the drug, but more slowly.

Paxil side effects:

Side effects are usually mild. With continued therapy, side effects decrease in intensity and frequency of occurrence and usually do not lead to discontinuation of treatment. The following criteria for assessing the incidence of adverse events were used: often (1% and<10%), нечасто (0.1% и <1%), редко (0.01% и <0.1%), очень редко (<0.01%), включая отдельные случаи. Встречаемость частых и нечастых побочных эффектов была определена на основании обобщенных данных о безопасности применения препарата более чем у 8000 человек, участвовавших в клинических испытаниях (ее раcсчитывали по разнице между частотой побочных эффектов в группе пароксетина и в группе плацебо). Встречаемость редких и очень редких побочных эффектов определяли на основании постмаркетинговых данных (касается скорее частоты сообщений о таких эффектах, чем истинной частоты самих эффектов).

From the digestive system: very often - nausea, loss of appetite; often - dry mouth, constipation, diarrhea; rarely - increased levels of liver enzymes; very rarely - gastrointestinal bleeding, hepatitis (sometimes with jaundice), liver failure (with the development of side effects from the liver, the question of the advisability of stopping therapy should be considered in cases where there is a prolonged increase in functional tests).

From the side of the central nervous system: often - drowsiness, tremor, asthenia, insomnia, dizziness; infrequently - confusion, hallucinations, extrapyramidal symptoms; rarely - mania, convulsions, akathisia; very rarely - serotonin syndrome (agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, tachycardia, tremor). In patients with motor disorders or taking antipsychotics - extrapyramidal disorders with orofacial dystonia.

On the part of the organ of vision: often - blurred vision; very rarely - acute glaucoma.

From the side of the cardiovascular system: infrequently - a transient increase or decrease in blood pressure (usually in patients with arterial hypertension and anxiety), sinus tachycardia; very rarely - peripheral edema.

From the urinary system: rarely - urinary retention.

From the blood coagulation system: infrequently - hemorrhages in the skin and mucous membranes, bruising; very rarely - thrombocytopenia.

From the endocrine system: rarely - hypoprolactinemia / galactorrhea and hyponatremia (mainly in elderly patients), which is sometimes caused by a syndrome of insufficient secretion of antidiuretic hormone.

Allergic reactions: very rarely - angioedema, urticaria; rarely - skin rash.

Others: very often - sexual dysfunction; often - increased sweating, yawning; very rarely - photosensitivity reactions.

Undesirable symptoms observed during clinical trials in children

In clinical trials in children, the following side effects occurred in 2% of patients and occurred 2 times more often than in the placebo group: emotional lability (including self-harm, suicidal thoughts, suicidal attempts, tearfulness, mood lability) , hostility, decreased appetite, tremor, increased sweating, hyperkinesia and agitation. Suicidal thoughts, suicidal attempts were mainly observed in clinical trials in adolescents with severe depressive disorder, in which the effectiveness of paroxetine has not been proven. Hostility has been reported in children (especially those under 12 years of age) with OCD.

Contraindications to the drug:

Simultaneous administration of MAO inhibitors and a period of 14 days after their withdrawal (MAO inhibitors cannot be prescribed within 14 days after the end of treatment with paroxetine);

Simultaneous reception of thioridazine;

Hypersensitivity to paroxetine and other components of the drug.

Use during pregnancy and lactation.

In experimental studies, no teratogenic or embryotoxic effects of paroxetine have been identified. Data from a small number of women who took paroxetine during pregnancy suggest no increased risk of congenital anomalies in newborns.

There are reports of premature birth in women who received paroxetine during pregnancy, but a causal relationship with the drug has not been established. Paxil should not be used during pregnancy unless the potential benefit of treatment outweighs the possible risk associated with taking the drug.

It is necessary to monitor the health of newborns whose mothers took paroxetine in late pregnancy, since there are reports of complications in children (however, a causal relationship with the drug has not been established). Respiratory distress syndrome, cyanosis, apnea, convulsive seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, arterial hyper- or hypotension, hyperreflexia, tremor, irritability, lethargy, constant crying, drowsiness are described. In some reports, the symptoms have been described as neonatal manifestations of the withdrawal syndrome. In most cases, the described complications occurred immediately after childbirth or shortly after them (within 24 hours).

Paroxetine is excreted in small amounts in breast milk. Therefore, the drug should not be used during lactation, unless the potential benefit of treatment outweighs the possible risk associated with taking the drug.

Special instructions for the use of Paxil.

Patients with depression may experience exacerbation of symptoms and/or the emergence of suicidal thoughts and behavior (suicidality) regardless of whether they receive antidepressants. This risk persists until a marked remission is achieved. There may be no improvement in the patient's condition in the first weeks of treatment or more, so the patient must be carefully monitored for the timely detection of a clinical exacerbation of suicidal tendencies, especially at the beginning of the course of treatment, as well as during periods of dose changes (increase or decrease). Clinical experience with all antidepressants indicates that the risk of suicide may increase in the early stages of recovery.

Other psychiatric disorders treated with paroxetine may also be associated with an increased risk of suicidal behavior. In addition, these disorders may be comorbid conditions associated with major depressive disorder. Therefore, in the treatment of patients suffering from other mental disorders, the same precautions should be observed as in the treatment of major depressive disorder.

Patients with a history of suicidal behavior or suicidal thoughts, younger patients, and patients with severe suicidal thoughts before treatment are at greatest risk of suicidal thoughts or suicidal attempts, and therefore all of them need to be given special attention during treatment. Patients (and caregivers) should be warned to watch for worsening of their condition and/or the appearance of suicidal thoughts/suicidal behavior or thoughts of harming themselves and seek immediate medical attention if these symptoms occur.

Sometimes treatment with paroxetine is accompanied by the occurrence of akathisia, which is manifested by a feeling of inner restlessness and psychomotor agitation, when the patient cannot sit or stand still; in akathisia, the patient usually experiences subjective distress. The chance of akathisia occurring is highest in the first few weeks of treatment.

In rare cases, serotonin syndrome or neuroleptic malignant syndrome-like symptoms (hyperthermia, muscle rigidity, myoclonus, autonomic disorders with possible rapid changes in vital signs, changes in mental status, including confusion, irritability, extremely severe agitation) may occur during treatment with paroxetine. progressing to delirium and coma), especially if paroxetine is used in combination with other serotonergic drugs and/or antipsychotics. These syndromes are potentially life-threatening, so if they occur, treatment with paroxetine should be discontinued and supportive symptomatic therapy initiated. Given this, paroxetine should not be administered in combination with serotonin precursors (such as L-tryptophan, oxytriptan) due to the risk of developing serotonin syndrome.

A major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although not proven by controlled clinical trials) that treating such an episode with an antidepressant alone may increase the likelihood of an accelerated mixed/manic episode in patients at risk for bipolar disorder.

Before initiating antidepressant treatment, a thorough screening should be performed to assess the patient's risk of developing bipolar disorder; such screening should include a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression. Like all antidepressants, paroxetine is not registered for the treatment of bipolar depression. Paroxetine should be used with caution in patients with a history of mania.

Treatment with paroxetine should be started cautiously, not earlier than 2 weeks after stopping therapy with MAO inhibitors; the dose of paroxetine should be increased gradually until the optimal therapeutic effect is achieved.

The frequency of seizures in patients taking paroxetine is less than 0.1%. If a seizure occurs, treatment with paroxetine should be discontinued.

There is only limited experience with the concomitant use of paroxetine and electroconvulsive therapy.

Bleeding into the skin and mucous membranes (including gastrointestinal bleeding) has been reported in patients taking paroxetine. Therefore, paroxetine should be used with caution in patients who are concomitantly receiving drugs that increase the risk of bleeding, in patients with a known bleeding tendency, and in patients with diseases that predispose to bleeding.

After discontinuation of the drug (especially abrupt), dizziness, sensory disturbances (paresthesia), sleep disturbances (vivid dreams), anxiety, headache, infrequently - agitation, nausea, tremor, confusion, increased sweating, diarrhea. In most patients, these symptoms were mild or moderate, but in some patients they may be severe. Usually, withdrawal symptoms occur in the first few days after discontinuation of the drug, but in rare cases - after an accidental skipping of one dose. As a rule, these symptoms disappear on their own within two weeks, but in some patients - up to 2-3 months or more. Therefore, it is recommended to gradually reduce the dose of paroxetine (over several weeks or months before completely canceling it, depending on the needs of the patient).

The occurrence of withdrawal symptoms does not mean that the drug is addictive.

In children, symptoms of paroxetine withdrawal (emotional lability, suicidal thoughts, suicidal attempts, mood changes, tearfulness, nervousness, dizziness, nausea, abdominal pain) were observed in 2% of patients on the background of a reduction in the dose of paroxetine or after its complete withdrawal and occurred 2 times more often than in the placebo group.

The drug should be used with caution in liver failure, renal failure, angle-closure glaucoma, heart disease, epilepsy.

If the increase in the level of liver enzymes observed during the use of Paxil persists for a long time, the drug should be discontinued.

Paxil does not potentiate the effect of alcohol on psychomotor functions, however, patients taking Paxil are advised to refrain from drinking alcohol.

Pediatric use

Paroxetine is not prescribed to children under the age of 7 years due to the lack of data on the safety and efficacy of the drug in this category of patients.

Controlled clinical studies on the use of paroxetine for the treatment of depression in children and adolescents aged 7 to 18 years have not proven its effectiveness, therefore the drug is not indicated for use in this age group.

In clinical trials, adverse events associated with suicidality (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, deviant behavior and anger) were more frequently observed in children and adolescents treated with paroxetine than in those patients of this age group who received placebo. There are currently no data on the long-term safety of paroxetine in children and adolescents regarding the effect of the drug on growth, maturation, cognitive and behavioral development.

Influence on the ability to drive vehicles and control mechanisms

Paxil therapy does not cause cognitive impairment or psychomotor retardation. However, as with any psychotropic medication, patients should exercise caution when driving and operating machinery.

Drug overdose:

Available information on paroxetine overdose suggests a wide range of safety.

Symptoms: increased side effects described above, as well as vomiting, dilated pupils, fever, changes in blood pressure, involuntary muscle contractions, agitation, anxiety, tachycardia. Patients usually do not develop serious complications even with a single dose of up to 2 g of paroxetine. In some cases, coma and EEG changes develop, and very rarely death occurs when paroxetine is combined with psychotropic drugs or alcohol.

Treatment: standard measures used in case of an overdose of antidepressants (gastric lavage through artificial vomiting, the appointment of 20-30 mg of activated charcoal every 4-6 hours during the first day after an overdose). The specific antidote is unknown. Supportive therapy and control of vital body functions are shown.

Interaction of Paxil with other drugs.

absorption and

Pharmacokinetics of the drug.

paroxetine are not changed at all or only partially changed under the influence of food, antacids, digoxin, propranolol and ethanol.

With the simultaneous use of Paxil with MAO inhibitors, L-tryptophan, triptans, tramadol, linezolid, drugs of the group of selective serotonin reuptake inhibitors, lithium, preparations of St. John's wort, serotonin syndrome may develop.

Metabolism and pharmacokinetic parameters of Paxil may change with the simultaneous use of drugs that induce or inhibit protein metabolism. With the simultaneous use of Paxil with drugs that inhibit the metabolism of enzymes, the doses used should be limited to the lower limit of the usual level. When combined with drugs that induce the metabolism of enzymes (carbamazepine, phenytoin, rifampicin, phenobarbital), no change in the initial doses of Paxil is required. Subsequent dose adjustment should be carried out depending on the clinical effect.

With the simultaneous use of Paxil with drugs metabolized by the CYP2D6 isoenzyme (tricyclic antidepressants / amitriptyline, nortriptyline, imipramine, desipramine /, phenothiazine neuroleptics / thioridazine, perphenazine /, class IC antiarrhythmic drugs / propafenone, flecainide and metoprolol /, risperidone), there is an increase in their concentrations in blood plasma.

The combination of Paxil with terfenadine, alprazolam and other drugs that are substrates for the CYP3A4 isoenzyme does not cause adverse reactions.

Daily administration of Paxil significantly increases plasma levels of procyclidine. In the presence of anticholinergic symptoms, the dose of procyclidine should be reduced.

Paxil does not potentiate the effect of ethanol on psychomotor functions, however, patients taking Paxil are advised to refrain from taking ethanol-containing drugs.

With the simultaneous use of Paxil with epilepsy with anticonvulsants (carbamazepine, phenytoin, sodium valproate), there was no effect on the pharmacokinetics and pharmacodynamics of the latter.

Unlike antidepressants, which inhibit norepinephrine reuptake, paroxetine suppresses the antihypertensive effects of guanethidine much weaker.

With simultaneous use with short-acting hypnotic drugs, no additional side effects were noted.

Conditions of sale in pharmacies.

The drug is dispensed by prescription.

Terms of the storage conditions of the drug Paxil.

The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life - 3 years.

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