Paroxetine - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate dihydrate - 209.73 mg; microcrystalline cellulose - 60,00 mg; sodium carboxymethyl starch - 3.00 mg; silicon dioxide colloidal - 1,50 mg; magnesium stearate - 3.00 mg.

Shell composition: hypromellose - 4,54 mg; Macrogol-4000 - 1.06 mg; titanium dioxide - 2.40 mg.

Composition per tablet 30 mg:

Active substance: paroxetine hydrochloride hemihydrate - 34.15 mg, in terms of paroxetine - 30,00 mg.

Excipients: calcium hydrophosphate dihydrate - 314,60 mg; microcrystalline cellulose - 90,00 mg; sodium carboxymethyl starch - 4.50 mg; silicon dioxide colloidal - 2.25 mg; magnesium stearate - 4.50 mg.

Shell composition: hypromellose - 6.81 mg; Macrogol-4000 - 1.59 mg; titanium dioxide - 3.60 mg.

Description:TOrifle, biconvex tablets with a risk on one side, covered with a film shell of white or almost white color

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.B Selective serotonin reuptake inhibitors

N.06.A.B.05 Paroxetine

Pharmacodynamics:

Mechanism of action

Paroxetine is a potent and selective 5-hydroxytryptamine reuptake inhibitor (5-HT, serotonin). It is believed that its antidepressant activity and effectiveness in the treatment of obsessive-compulsive (OCD) and panic disorder is due to the specific inhibition of reuptake of serotonin in neurons of the brain.

By its chemical structure paroxetine differs from tricyclic, tetracyclic and other known antidepressants.

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

In accordance with the selective effect of paroxetine, studies in vitro showed that, unlike tricyclic antidepressants, it has a weak affinity for α₁, α₂- and βadrenoreceptors, as well as dopamine (D₂), 5-HT₁-like, 5HT₂- and histamine (H₁) receptors. This lack of interaction with postsynaptic receptors in vitro is confirmed by the results of studies in vivo, which demonstrated the lack of paroxetine ability to oppress the central nervous system (CNS) and cause arterial hypotension.

Pharmacodynamic effects

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

Like other selective serotonin reuptake inhibitors, paroxetine causes symptoms of excessive stimulation of 5-HT-receptors when administered to animals that previously received monoamine oxidase (MAO) inhibitors or tryptophan.

Studies of EEG behavior and changes demonstrated that paroxetine causes mild activating effects at doses in excess of those required to inhibit serotonin reuptake. By its very nature, its activating properties are not "amphetamine-like".

Studies in animals have shown that paroxetine does not affect the cardiovascular system.

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

Studies have shown that, unlike antidepressants, which seizure of norepinephrine, paroxetine has a much lower ability to inhibit antihypertensive effects of guanethidine.

Pharmacokinetics:

Absorption

After oral administration paroxetine it is well absorbed and subjected to the metabolism of the "first passage".

Due to the metabolism of the "first passage", less paroxetine is delivered to the systemic bloodstream than that absorbed from the gastrointestinal tract. As the amount of paroxetine increases in the body with a single dose of large doses or with repeated intake of usual doses, a partial saturation of the metabolic path of the "first passage" occurs and the clearance of paroxetine from the plasma decreases. This leads to a disproportionate increase in the concentrations of paroxetine in the plasma. Therefore, its pharmacokinetic parameters are not stable, resulting in nonlinear kinetics.It should be noted, however, that the nonlinearity is usually poorly expressed and is observed only in those patients who, when taking low doses of the drug in the plasma, achieve low levels of paroxetine. Stable concentrations in the plasma are reached 7-14 days after the start of paroxetine treatment, its pharmacokinetic parameters most likely do not change during prolonged 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 the plasma. At therapeutic concentrations, approximately 95% of paroxetine in the plasma is associated with proteins.

There was no correlation between paroxetine concentrations in plasma and its clinical effect (ie, with adverse reactions and efficacy). Determined that paroxetine in small quantities penetrates into the breast milk of women, as well as in embryos and fruits of laboratory animals.

Metabolism

The main metabolites of paroxetine are polar and conjugated oxidation and methylation products, which are easily eliminated from the body.Given the relative lack of pharmacological activity in these metabolites, it can be argued that they do not affect the therapeutic effects of paroxetine.

Metabolism does not impair the ability of paroxetine to selectively inhibit the reverse seizure of serotonin.

Elimination

With urine in the form of unchanged paroxetine excreted less than 2% of the dose, while excretion of metabolites reaches 64% of the dose. About 36% of the dose is excreted with feces, probably getting into it with bile; Excretion with feces of unchanged paroxetine is less than 1% of the dose. In this way, paroxetine is eliminated almost entirely by metabolism.

Excretion of metabolites is biphasic in nature: first it is the result of the metabolism of the "first passage", then it is controlled by systemic elimination of paroxetine.

The half-life of paroxetine varies, but usually is about 1 day (16-24 hours).

Indications:

Depression

Depression of all types, including reactive and severe depression, as well as depression, accompanied by anxiety.

In the treatment of depressive disorders paroxetine has approximately the same efficacy as tricyclic antidepressants. There is evidence that paroxetine can give good results in patients in whom standard antidepressant therapy has proven ineffective.

Taking paroxetine in the morning does not adversely affect the quality and duration of sleep. In addition, as the effect of paroxetine treatment appears, sleep can improve.

When using short-acting hypnotic drugs in combination with antidepressants, no additional side effects occurred. In the first few weeks of therapy paroxetine effectively reduces the symptoms of depression and suicidal thoughts.

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

Obsessive-compulsive disorder

Paroxetine is effective in the treatment of obsessive-compulsive disorder (ROC), including. and as a means of supporting and prophylactic therapy. Besides, paroxetine effectively prevented the recurrence of OCD.

Panic disorder

Paroxetine is effective in the treatment of panic disorder with and without agoraphobia, incl. as a means of supporting and prophylactic therapy.It has been established that in the treatment of panic disorder, the combination of paroxetine and cognitive-behavioral therapy is significantly more effective than the isolated application of cognitive-behavioral therapy.

Besides, paroxetine effectively prevented the recurrence of panic disorder.

Social phobia

Paroxetine is an effective treatment for social phobia, incl. and as a long-term maintenance and prophylactic therapy.

Generalized anxiety disorder

Paroxetine is effective in generalized anxiety disorder, incl. and as a long-term maintenance and prophylactic therapy. Paroxetine also effectively prevents relapses in this disorder.

Post-Traumatic Stress Disorder

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

Contraindications:

- Hypersensitivity to paroxetine and any other component included in the preparation;

- paroxetine contraindicated in combination with monoamine oxidase inhibitors (MAOI). In exceptional cases linezolid (an antibiotic that is a reversible non-selective MAOI) is allowed to be combined with paroxetine provided that acceptable alternatives to linezolid treatment are not available and the potential use of linezolid outweighs the risks of serotonin syndrome or malignant neuroleptic syndrome, as reactions in a particular patient.

Equipment for careful monitoring of symptoms of serotonin syndrome and monitoring of blood pressure should be available. Paroxetine treatment is allowed:

2 weeks after discontinuation of treatment with irreversible MAOI or
at least 24 hours after discontinuation of treatment with reversible MAOIs (eg, moclobemide, linezolid, megylthioninium chloride (methylene blue)),
must undergo at least 1 week between the abolition of paroxetine and the initiation of therapy by any MAOI;

- combined use with thioridazine. Paroxetine should not be used in combination with thioridazine, because, like other drugs that inhibit hepatic isoenzyme activity CYP2D6, paroxetine may increase the concentration of thioridazine in the plasma, which may lead to lengthening of the interval QTc and associated ventricular arrhythmias such as "pirouettes", potentially life-threatening, and sudden death;

- combined use with pimozide;

- use in children and adolescents under 18 years of age. Controlled clinical studies of paroxetine in the treatment of depression in children and adolescents have not proven its effectiveness, so the drug is not indicated for treatment of this age group. The safety and efficacy of paroxetine have not been studied in patients younger than 7 years of age.

Pregnancy and lactation:

Fertility

According to animal studies paroxetine can affect the qualitative characteristics of sperm.

Data from the study of human material in vitro may indicate some effect on the qualitative characteristics of sperm, however, in reports of cases of use in humans of some preparations of SSRI inhibitors (including paroxetine) it was shown that the influence on the qualitative characteristics of sperm turned out to be reversible.

Until now, there has been no effect on human fertility.

Pregnancy

Studies in animals have not revealed teratogenic or selective embryotoxic activity in paroxetine.

Epidemiological studies of pregnancy outcomes when taking antidepressants in the first trimester revealed an increased risk of congenital anomalies, in particular, the cardiovascular system (eg, interventricular and atrial septal defects) associated with paroxetine. According to available data, the occurrence of cardiovascular system defects with paroxetine during pregnancy is approximately 1/50, whereas the expected occurrence of such defects in the general population is approximately 1/100 of the newborns. When the appointment of paroxetine should consider the possibility of alternative treatment for pregnant women and pregnant women planning pregnancy. Paroxetine should be appointed only if its potential benefit exceeds the possible risk. If a decision is made to discontinue paroxetine during pregnancy, the physician should follow the recommendations of the "Dosage and Administration" section - "Paroxetine withdrawal" and "Special instructions" - "Symptoms that may occur when discontinuing paroxetine treatment in adults."

There are reports of premature birth in women who received during pregnancy paroxetine or other drugs of the SSRI group, but the causal relationship between taking these drugs and premature birth is not established. It is necessary to monitor the health status of those newborns whose mothers have taken paroxetine in late pregnancy, because there are reports of complications in newborns exposed to paroxetine or other SSRI drugs in the third trimester of pregnancy. However, the causal relationship between the complications mentioned and this drug therapy is not confirmed. The clinical complications described included: respiratory distress syndrome, cyanosis, apnea, convulsive seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, arterial hypertension, arterial hypotension, hyperreflexia, tremor, irritability, lethargy, persistent crying and drowsiness. In some reports, the symptoms have been described as neonatal manifestations of withdrawal syndrome. In most cases, the described complications occurred immediately after birth or shortly after birth (<24 h).According to epidemiological studies, the intake of SSRIs (including paroxetine) during pregnancy, especially in later periods, is associated with an increased risk of developing persistent pulmonary hypertension in newborns. The increased risk is observed in children born to mothers who took SSRI drugs in late pregnancy, and 4-5 times higher than the observed in the general population (1-2 per 1,000 pregnancies).

The results of animal studies showed reproductive toxicity of the drug, but no direct adverse effect on pregnancy, embryo and fetal development, labor or postnatal development has been shown.

Breastfeeding period

In breast milk penetrate a small number paroxetine. In published studies in infants breastfed, the concentration of paroxetine was undetectable (<2 ng / ml) or very low (<4 ng / ml).

Children showed no signs of drug exposure. Nevertheless paroxetine should not be taken during breastfeeding, except when its benefit to the mother exceeds the potential risks to the child.

Dosing and Administration:

Paroxetine is recommended to be taken 1 time a day in the morning during a meal. The tablet should be swallowed whole, without chewing.

Depression

The recommended dose for adults is 20 mg per day. If necessary, depending on the therapeutic effect, the daily dose may increase weekly by 10 mg per day to a maximum dose of 50 mg per day. As with any antidepressant treatment, the effectiveness of therapy should be evaluated and, if necessary, the dose of paroxetine should be adjusted 2-3 weeks after the start of treatment and in the future, depending on the clinical indications.

To relieve depressive symptoms and prevent relapses, adequate duration of stopping and maintenance therapy should be observed. This period can be several months.

Obsessive-compulsive disorder

The recommended dose is 40 mg per day. Treatment begins with a dose of 20 mg per day, which can be increased weekly by 10 mg per day. If necessary, the dose can be increased to 60 mg per day. It is necessary to observe adequate duration of therapy (several months and longer).

Panic disorder

The recommended dose is 40 mg per day. Treatment of patients should begin with a dose of 10 mg per day and weekly increase the dose by 10 mg per day, focusing on the clinical effect. If necessary, the dose may be increased to 60 mg per day. A low initial dose is recommended to minimize the possible increase in symptoms of panic disorder, which can occur at the beginning of treatment with any antidepressant. It is necessary to observe adequate periods of therapy (several months and longer).

Social phobia

The recommended dose is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day, depending on the clinical effect to 50 mg per day.

Generalized anxiety disorder

The recommended dose is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day, depending on the clinical effect to 50 mg per day.

Post-Traumatic Stress Disorder

The recommended dose is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day, depending on the clinical effect to 50 mg per day.

general information

Paroxetine withdrawal

As in the treatment of other psychotropic drugs, avoid abrupt withdrawal of paroxetine.

The following cancellation schedule can be recommended: reduction of the daily dose by 10 mg per week; after reaching a dose of 20 mg / day patients continue to take this dose for 1 week, and only after that the drug is canceled completely. If withdrawal symptoms develop during dose reduction or after drug withdrawal, it is advisable to resume taking the previously prescribed dose. In the future, the doctor may continue to reduce the dose, but more slowly.

Individual patient groups

Elderly patients

In elderly patients, paroxetine concentrations in the blood plasma can be increased, but the range of its plasma concentrations coincides with those in younger patients. In this category of patients, therapy should be started with a dose recommended for adults, which can be increased to 40 mg per day.

Patients with impaired renal or hepatic function

Paroxetine concentrations in the blood plasma are elevated in patients with severe renal impairment (creatinine clearance less than 30 ml / min) and in patients with impaired liver function.Such patients should be given doses of the drug that are in the lower part of the therapeutic dose range.

Children and teenagers (under the age of 18)

The use of paroxetine in children and adolescents (under 18 years of age) is contraindicated.

Side effects:

The frequency and intensity of some of the undesirable reactions of paroxetine listed below may decrease as the treatment continues, and such reactions usually do not require withdrawal of the drug.

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥1/10), often (≥1/100, ≥1/10), infrequently (≥1/1000, ≥1/100), rarely (≥1/10000, ≥1/1000), rarely (≥1 / 10000), including individual cases, and frequency is unknown.

The incidence of frequent and infrequent adverse reactions was determined based on general safety data for more than 8,000 patients participating in clinical trials and was calculated from the difference between the incidence of adverse reactions in the paroxetine group and the placebo group. The occurrence of rare and very rare undesirable reactions was determined on the basis of postmarketing data, and it refers more to the frequency of reports of such reactions than to the true frequency of the reactions themselves.

On the part of the hematopoiesis system: infrequently - abnormal bleeding, mainly hemorrhage into the skin and mucous membranes (most often - bruising); very rarely - thrombocytopenia.

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

From the endocrine system: rarely - syndrome of disturbed secretion of antidiuretic hormone.

Disorders from the metabolism and nutrition: often - decreased appetite, increased cholesterol concentration; rarely - hyponatremia. Hyponatremia occurs mainly in elderly patients and may be due to the syndrome of impaired secretion of antidiuretic hormone.

Mental disorders: often - drowsiness, insomnia, agitation, unusual dreams (including nightmares); infrequently confusion, hallucinations; rarely - manic reactions, anxiety, depersonalization, panic attacks, akathisia; frequency unknown - Suicidal thoughts, suicidal behavior. Cases of suicidal thoughts and suicidal behavior were documented during treatment with paroxetine or in the early stages after discontinuation of treatment.These symptoms can also be caused by the disease itself.

From the nervous system: often - dizziness, tremor, headache, violation of concentration of attention; infrequently - extrapyramidal disorders; rarely convulsions, restless legs syndrome; very rarely - serotonin syndrome (symptoms may include agitation, confusion, increased sweating, hallucinations, hyperreflexia, myoclonus, tachycardia with tremors and tremors). In patients with impaired motor function or who received antipsychotics, infrequent development of extrapyramidal symptoms was rarely reported, including orofacial dystonia.

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

From the side of the organ of hearing and balance: frequency unknown - noise in ears.

From the side of the cardiovascular system: infrequently - sinus tachycardia, postural hypotension, short-term increase and lowering of blood pressure. Short-term increase and decrease in blood pressure were recorded after treatment with paroxetine, usually in patients with prior hypertension or anxiety; rarely - aetiology.

From the respiratory system: often - yawn.

From the gastrointestinal tract: Often - nausea; often - constipation, diarrhea, vomiting, dry mouth; rarely - gastrointestinal bleeding.

From the liver and biliary tract: rarely - increased activity of hepatic enzymes; rarely - hepatitis, sometimes accompanied with jaundice and / or liver failure.

Post-marketing messages of adverse reactions by the liver (such as hepatitis, sometimes accompanied with jaundice and / or liver failure) are very rare. The advisability of discontinuing treatment with paroxetine should be addressed in cases where there is prolonged elevation of indices of liver function tests.

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

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

From the side of the reproductive system and mammary glands: Often - sexual dysfunction; rarely - hyperprolactinaemia, galactorrhea, menstrual cycle disorders (including menorrhagia, metrorrhagia and amenorrhea); very rarely - priapism.

From the side of the musculoskeletal system: rarely - arthalgia, myalgia.

Epidemiological studies, mainly conducted in patients aged 50 years and older, showed an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism that leads to this risk is unknown.

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

Symptoms that occur when paroxetine is discontinued: often- dizziness, sensory disturbances, sleep disorders, anxiety, headache; infrequently - agitation, nausea, tremor, confusion, increased sweating, diarrhea, irritability.

A sharp discontinuation of the drug causes withdrawal syndrome. As with the abolition of many psychotropic drugs, discontinuing paroxetine treatment (especially severe) can cause symptoms such as dizziness, sensory disturbances (including paresthesia,sensation of discharge of electric current and noise in the ears), sleep disturbances (including bright 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 go away spontaneously. There is no known group of patients who would be at an increased risk of such symptoms; so if in the treatment of paroxetine is no longer necessary, its dose should be reduced slowly until the drug is completely discontinued.

Undesirable effects observed in clinical studies in children

The following undesirable reactions were observed: emotional lability (including self-harm, suicidal thoughts, suicidal attempts, tearfulness and mood swings), bleeding, hostility, decreased appetite, tremor, increased sweating, hyperkinesia, and agitation.

Suicidal thoughts and suicidal attempts were mainly observed in clinical studies in adolescents with major depressive disorder.

Hostility was noted in children with obsessive-compulsive disorder, especially in children younger than 12 years.

In clinical studies, a gradual decrease in the daily dose (daily dose was reduced by 10 mg per day with an interval of one week to a dose of 10 mg per day for one week) caused symptoms of paroxetine withdrawal (emotional lability, nervousness, dizziness, nausea and abdominal pain) that were registered in at least 2% of patients on the background of a decrease in the dose of paroxetine or after its complete withdrawal and met at least 2 times more often than in the placebo group.

Overdose:

Objective and subjective symptoms

The available information on paroxetine overdose testifies to its wide range of safety. In case of paroxetine overdose, in addition to the symptoms described in the "Side effect" section, fever, changes in blood pressure, involuntary muscle contractions, anxiety and tachycardia are observed.

The condition of patients usually normalized without serious consequences, even with a single dose of up to 2000 mg. A number of reports described symptoms such as coma, and ECG changes, deaths were very rare, usually in situations where patients received paroxetine together with other psychotropic drugs or with alcohol.

Treatment

There is no specific antidote of paroxetine. Treatment should consist of general measures used for an overdose of any antidepressant. Supportive therapy and frequent monitoring of basic physiological parameters are shown. The patient should be treated in accordance with the clinical picture or in accordance with the recommendations of the National Toxicology Center.

Interaction:

Serotonergic drugs

The use of paroxetine, as well as other drugs of the SSRI group, simultaneously with serotonergic drugs (including L-tryptophan, triptans, tramadol, preparations of the SSRIs group, fentanyl, lithium and herbal remedies containing St. John's wort) may cause effects associated with 5-HT (serotonin syndrome), caution should be exercised and careful clinical monitoring performed. Simultaneous use of paroxetine with MAO inhibitors (including linezolid - an antibiotic that transforms into a nonselective MAO inhibitor, and methylthioninium chloride (methylene blue)) is contraindicated.

Pimozide

In the study, the feasibility of sharing paroxetine and pimozide in a single low dose (2 mg) increased the level of pimozide. This fact is due to the known property of paroxetine to depress the CYP2D6 system. Due to the narrow therapeutic index of pimozide and its known ability to extend the QT interval, simultaneous use of pimozide and paroxetine is contraindicated.

Enzymes involved in the metabolism of drugs

Metabolism and pharmacokinetics of paroxetine can vary under the influence of induction or inhibition of enzymes that are involved in the metabolism of drugs.

When paroxetine is used simultaneously with inhibitors of enzymes involved in the metabolism of drugs, one should evaluate the feasibility of using a dose of paroxetine, located in the lower part of the therapeutic dose range. The initial dose of paroxetine should not be adjusted if it is used concomitantly with a drug that is a known inducer of enzymes involved in the metabolism of drugs (for example, carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent correction of the dose of paroxetine should be determined by its clinical effects (tolerability and efficacy).

Fosamprenavir / ritonavir

Simultaneous use of fosamprenavir / ritonavir with paroxetine led to a significant decrease in the concentration of paroxetine in the blood plasma. Concentrations of fosamprenavir / ritonavir in plasma with simultaneous use with paroxetine were similar to control values from other studies, indicating that there is no significant effect of paroxetine on the metabolism of fosamprenavir / ritonavir. Data on the effects of long-term combined use of paroxetine with fosamprenavir / ritonavir are not available. Any subsequent correction of the dose of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Procyclidine

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

Anticonvulsants

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

Neuromuscular blockers

Preparations of the SSRI group can reduce the activity of cholinesterase of the blood plasma, which leads to an increase in the duration of the neuromuscular blocking effect of myovacury and suxamethonium.

The ability of paroxetine to inhibit isoenzyme CYP2D6

Like other antidepressants, including other SSRIs, paroxetine inhibits the hepatic enzyme CYP2D6, related to the cytochrome P450 system. Inhibition of enzyme CYP2D6 can lead to an increase in plasma concentrations of concomitantly used drugs that are metabolized by this enzyme. These drugs include some tricyclic antidepressants (for example, amitriptyline, nortriptyline, imipramine and desipramine), neuroleptics of the phenothiazine series (perphenazine and thioridazine), risperidone, atomoxetine, some antiarrhythmic drugs of class 1 C (for example, propafenone and flecainide) and metoprolol.

It is not recommended to apply paroxetine in combination with metoprolol in heart failure, due to the narrow therapeutic index of metoprolol at this indication for use.

Irreversible inhibition of the system CYP2D6 paroxetine can lead to a decrease in the concentration of its active metabolite - endoxifene in the blood plasma, and as a consequence, reduce the effectiveness of tamoxifen.

The ability of paroxetine to inhibit isoenzyme CYP3A4

Investigation of interaction in vivo when the paroxetine and terfenadine, which is a substrate of the isoenzyme, are simultaneously applied, under equilibrium conditions, CYP3A4, showed that paroxetine does not affect the pharmacokinetics of terfenadine. In a similar interaction study in vivo There was no effect of paroxetine on the pharmacokinetics of alprazolam, and vice versa. Simultaneous use of paroxetine with terfenadine, alprazolam and other drugs that serve as a substrate for isoenzyme CYP3A4, can hardly cause harm to the patient. Clinical studies have shown that the absorption and pharmacokinetics of paroxetine is independent or practically independent (i.e., the existing dependence does not require a dose change) from food, antacids, digoxin, propranolol, alcohol (paroxetine It does not increase the negative effect of ethanol on psychomotor functions, but not It is recommended to take paroxetine and alcohol).

Oral anticoagulants

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

NSAIDs, acetylsalicylic acid and other antiplatelet drugs

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

Caution must be exercised in the treatment of patients receiving SSRI drugs simultaneously with oral anticoagulants, with drugs that affect platelet function or increase the risk of bleeding (e.g., atypical antipsychotics, such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, NSAIDs, COX-2 inhibitors), as well as in the treatment of patients who have a history of blood clotting disorders or conditions that may cause a predisposition to bleeding.

Special instructions:

Children and teenagers (under the age of 18)

A drug Paroxetine Do not use in children and adolescents under 18 years of age.

Treatment with antidepressants for children and adolescents with major depressive disorder and other mental illnesses is associated with an increased risk of suicidal thoughts and suicidal behavior. In clinical trials, adverse reactions associated with suicidal attempts and suicidal thoughts, hostility (mainly aggression, deviant behavior and anger) were more common in children and adolescents who received paroxetine, than in patients of this age group who received a placebo. At present, there is no data on the long-term safety of paroxetine for children and adolescents, which would affect the effect of this drug on growth, maturation, cognitive and behavioral development.

Clinical deterioration and suicidal risk in adults

Young patients, especially those suffering from major depressive disorder, may be at increased risk of suicidal behavior during paroxetine therapy. An analysis of placebo-controlled studies in adults with mental illnesses indicates an increase in the incidence of suicidal behavior in young patients (aged 18-24 years) when taking paroxetine compared to the placebo group (2.19% to 0.92%, respectively ), although this difference is not considered statistically significant. In patients of older age groups (25 to 64 years and older than 65 years), there was no increase in the incidence of suicidal behavior. In adults of all age groups suffering from major depressive disorder, there was a statistically significant increase in cases of suicidal behavior against paroxetine compared with the placebo group (the incidence of suicidal attempts: 0.32% to 0.05%, respectively). However, most of these cases, when taking paroxetine (8 of 11), were registered in young patients aged 18 to 30 years. Data obtained in the study in patients with major 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 psychiatric disorders. In patients with depression, the exacerbation of symptoms of this disorder and / or the appearance of suicidal thoughts and suicidal behavior (suicidal) can be observed regardless of whether they receive antidepressants. This risk persists until a pronounced remission is achieved. Improvement of the patient's condition may be absent in the first weeks of treatment or more, and therefore, the patient's condition should be carefully monitored in order to detect clinical exacerbation and suicidality in a timely manner, especially at the beginning of the course of treatment, as well as during periods of dose changes, whether they increase or decrease. Clinical experience with the use of all antidepressants shows that the risk of suicide may increase in the early stages of recovery. Other mental disorders for which treatment is used paroxetine, too, may be associated with an increased risk of suicidal behavior.In addition, these disorders can be comorbid conditions associated with a major depressive disorder. Therefore, in treating patients suffering from other mental disorders, the same precautions should be followed as in the treatment of major depressive disorder.

The greatest risk of suicidal ideation or suicide attempts is patients with a history of suicidal behavior or suicidal thoughts, young patients, and patients with severe suicidal thoughts prior to treatment, and therefore all need to be given special attention during treatment. Patients (and those who care for them) should be warned about the need to monitor their deterioration (including the development of new symptoms) and / or the appearance of suicidal thoughts / suicidal behavior or thoughts of self-harm during the course of treatment, especially at the beginning of treatment , during the change in the dose of the drug (increase and decrease). If these symptoms occur, seek medical help immediately.

It should be remembered that such symptoms as agitation, akathisia or mania may be associated with a major disease or be a consequence of the therapy used. If symptoms of clinical impairment (including development of new symptoms) and / or suicidal thoughts / behavior occur, especially if they suddenly appear, the severity of the manifestations increases, or if they are not part of the previous symptom complex in this patient, before drug cancellation.

Akathisia

Occasionally, treatment with paroxetine or another SSRI drug is accompanied by the appearance of akathisia, which is manifested by a feeling of inner anxiety and psychomotor agitation, when the patient can not sit or stand still; At akathisia the patient usually experiences subjective discomfort. The likelihood of akathisia is highest in the first few weeks of treatment.

Serotonin syndrome / malignant neuroleptic syndrome

In rare cases, against the background of paroxetine treatment, serotonin syndrome or symptomatology like a malignant neuroleptic syndrome may occur,especially if paroxetine are used in combination with other serotonergic drugs and / or antipsychotics. These syndromes pose a potential threat to life, and therefore treatment with paroxetine should be discontinued if they occur (they are characterized by groups of symptoms such as hyperthermia, muscle rigidity, myoclonus, autonomic disorders with possible rapid changes in vital signs, changes in mental status, including confusion consciousness, irritability, extremely hard agitation, progressing to delirium and coma), and begin supporting symptomatic therapy. Paroxetine should not be used in combination with serotonin precursors (such as L-tryptophan, oxytryptan) due to the risk of developing 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 development of a mixed / manic episode in patients at risk of bipolar disorder.Before starting treatment with an antidepressant, a thorough screening should be performed to assess the risk of a bipolar disorder in the patient; such screening should include the collection of a detailed psychiatric history, including data on the presence in the family of cases of suicide, bipolar disorder and depression. Paroxetine It is not registered for the treatment of a depressive episode in the context of bipolar disorder. Paroxetine should be used with caution in patients who have a history of mania.

Diabetes

In patients with diabetes mellitus, treatment with SSRIs may affect glycemic control. You may need to adjust the dose of insulin and / or oral hypoglycemic drugs.

MAO inhibitors

Treatment with paroxetine should be started cautiously no earlier than 2 weeks after discontinuation of therapy with MAO inhibitors; The dose of paroxetine should be increased gradually until an optimal therapeutic effect is achieved.

Impaired kidney or liver function

It is advisable to use caution in treating paroxetine in patients with severe renal impairment or in patients with impaired hepatic function.

Epilepsy

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

Convulsive seizures

Frequency of convulsive seizures in patients taking paroxetine, is less than 0.1%. In the event of a seizure, paroxetine should be discontinued.

Electroconvulsive therapy

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

Glaucoma

Like other SSRIs, paroxetine may cause mydriasis, and it should be used with caution in patients with closed-angle glaucoma.

Hyponatremia

In the treatment of paroxetine, hyponatremia occurs rarely and predominantly in elderly patients and is leveled after the withdrawal of paroxetine.

Bleeding

Hemorrhages in the skin and mucous membranes (including gastrointestinal and gynecological bleeding) have been reported in patients with paroxetine. therefore paroxetine Caution should be used with caution in patients who simultaneously receive drugs that increase the risk of bleeding in patients with a known tendency to bleeding and patients with diseases predisposing to bleeding.

Heart Disease

In the treatment of patients with heart disease, the usual precautionary measures should be observed.

Symptoms that may occur when discontinuing paroxetine treatment in adults

According to clinical studies in adults, the incidence of adverse reactions with paroxetine was 30%, while the incidence of adverse reactions in the placebo group was 20%. The onset of withdrawal symptoms does not mean that the drug is abused or addictive, as is the case with drugs and psychotropic substances. Describing withdrawal symptoms such as dizziness, sensory disturbances (including paresthesia, electric shock and tinnitus), sleep disorders (including bright dreams), agitation or anxiety, nausea, tremors, confusion, increased sweating, headaches 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, they occur in the first few days after the drug is discontinued, but in very rare cases there are patients who accidentally missed taking only one dose.As a rule, these symptoms pass spontaneously and disappear within 2 weeks, but in some patients they can last much longer (2-3 months or more). It is recommended to reduce the dose of paroxetine gradually, for several weeks or months before its complete cancellation, depending on the needs of the individual patient.

Symptoms that may occur when paroxetine is discontinued in children and adolescents

As a result of clinical studies in children and adolescents, the incidence of adverse reactions with paroxetine withdrawal was 32%, while the incidence of adverse reactions in the placebo group was 24%. Symptoms of paroxetine withdrawal (emotional lability, including suicidal thoughts, suicidal attempts, mood changes and tearfulness, as well as nervousness, dizziness, nausea and abdominal pain) were recorded in 2% of patients on the background of a decrease in the dose of paroxetine or after its complete withdrawal and were 2 times more common than in the placebo group.

Fractures of bones

Based on the results of epidemiological studies of the risk of bone fractures, bone fragility was associated with the use of antidepressants, including SSRIs.The risk was observed during the course of treatment with antidepressants and was the maximum at the beginning of the course of therapy. The possibility of bone fractures should be considered when using paroxetine.

Tamoxifen

Some studies have shown that the effectiveness of tamoxifen, measured as the ratio of breast cancer recurrence / lethality, decreases with co-administration with paroxetine, as a result of irreversible inhibition of the isoenzyme CYP2D6. Risk can increase with joint application for a long time. When tamoxifen is used to treat or prevent breast cancer, consideration should be given to the use of alternative antidepressants that do not inhibit the isoenzyme CYP2D6 or render it to a lesser extent.

Effect on the ability to drive transp. cf. and fur:

Clinical experience with paroxetine indicates that it does not impair cognitive and psychomotor functions. However, as with any other psychotropic medications, patients should be especially cautious when driving a car and working with mechanisms.

Although paroxetine does not increase the negative impact on psychomotor functions, it is not recommended to apply simultaneously paroxetine and alcohol.

Form release / dosage:

Tablets, film-coated, 20 mg and 30 mg.

Packaging:

By 7, 10, 14, 20, 25 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

10, 20, 30, 40, 50 or 100 tablets in cans of polyethylene terephthalate for medicinal products sealed with caps screwed on with the first opening or by a "push-turn" system of polypropylene or polyethylene or polypropylene cans for drugs sealed with lids pulled from control of the first opening from polyethylene or cans of polypropylene for medicines sealed with lids pulled with the control of the first opening of high pressure polyethylene.

One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package (pack) made of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003695

Date of registration:21.06.2016

Expiration Date:21.06.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp17.08.2016

Illustrated instructions

Instructions

Paroxetine (Paroxetine)