Paroxetine-SZ pills 20mg, 30pcs

Composition

1 film-coated tablet contains:

Active ingredient:

paroxetine hydrochloride hemihydrate-22.8 mg, in terms of paroxetine-20 mg;

excipients (core):

calcium hydrophosphate dihydrate-269.7 mg;

sodium carboxymethyl starch-3.0 mg;

magnesium stearate-3.0 mg;

colloidal silicon dioxide (aerosil) – 1.5 mg;

excipients (shell): hypromellose – 4.59 mg; polysorbate-80 (twin-80) – 1.91 mg; talc-1.53 mg; titanium dioxide E 171-0.97 mg

Pharmacological action

Pharmacotherapy group: antidepressant.

ATX code: N06AB05

Pharmacological properties

Pharmacodynamics

Mechanism of action

Paroxetine 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 is due to specific inhibition of 5-HT reuptake in brain neurons.

Paroxetine differs in its chemical structure from tricyclic, tetracyclic and other known antidepressants.

Paroxetine is characterized by 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 studies in vitro have shown that it is, in contrast to tricyclic antidepressants, is characterized by low affinity for the α-1, α-2 and β-adrenergic receptors as well as Dofaminum (D₂),5-HT₁-like,5 NT₂-, and histamine (H₁) receptors. The absence 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 (CNS) and does not cause arterial hypotension.

Pharmacodynamic properties

Paroxetine does not interfere with psychomotor functions and does not enhance the depressing effect of ethanol on the central nervous system.

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

Behavioral and EEG studies have shown that paroxetine produces weak activating effects at doses higher than those required to inhibit 5-HT reuptake. By its nature, its activating properties are not “amphetamine-like”.

Animal studies have shown good tolerability in relation to the cardiovascular system.

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

Studies have shown that unlike antidepressants that inhibit norepinephrine reuptake, paroxetine has much less ability to inhibit the antihypertensive effects of guanethidine.

Pharmacokinetics

Suction

After oral use, 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 large dose or with repeated use of conventional doses, partial saturation of the first-pass metabolic pathway occurs and the clearance of paroxetine from the blood plasma decreases. This leads to a disproportionate increase in plasma concentrations of paroxetine, so its pharmacokinetic parameters are not constant, resulting in nonlinear kinetics. However, the non-linearity of the kinetics is usually insignificant and is observed only in those patients who have low plasma concentrations of paroxetine against the background of taking low doses of the drug.

Steady-state systemic concentrations are reached 7-14 days after the start of treatment with paroxetine, its pharmacokinetic parameters, as a rule, do not 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 bound to proteins.

There was no correlation between the plasma concentration of paroxetine and its clinical effect (with adverse reactions and efficacy).

Metabolism

The main metabolites of paroxetine are polar and conjugated oxidation and methylation products, which are easily eliminated from the body. Due to the practical lack 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 act on 5-HT reuptake in neurons.

Deduction

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

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

The elimination half-life of paroxetine varies, but is usually about 1 day.

Special patient groups

Elderly patients, patients with impaired renal and hepatic function.

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 concentrations in the blood plasma coincides with that in healthy adults.

Indications

• Moderate to severe depressive episodes
• Recurrent depressive disorder

The results of studies in which patients took paroxetine for up to 1 year indicate that it effectively prevents relapses and the return of symptoms of depression.

• Obsessive-compulsive disorder

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

According to placebo-controlled studies, the effectiveness of paroxetine in the treatment of OCD was maintained for at least 1 year. In addition, paroxetine effectively prevents relapses of OCD.

• Panic disorder

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

It was found that in the treatment of panic disorder, the combination of paroxetine and cognitive behavioral therapy is significantly more effective than the isolated use of cognitive behavioral therapy.

According to placebo-controlled studies, the effectiveness of paroxetine in the treatment of panic disorder was maintained for more than 1 year. In addition, paroxetine effectively prevented relapses of panic disorder.

• Social phobia

Paroxetine is effective in the treatment of social phobia, including as a long-term maintenance and preventive therapy.

The consistent effectiveness of paroxetine in the long-term treatment of social phobia was demonstrated in a relapse prevention study.

• Generalized anxiety disorder

Paroxetine is effective in the treatment of generalized anxiety disorder, including as a long-term maintenance and preventive therapy.

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

• Post-traumatic stress disorder

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

Use during pregnancy and lactation

Fertility

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

Data from an in vitro study of human material may indicate some effect on the quality characteristics of semen, but reports of human use of certain SSRI drugs (including paroxetine) have shown that the effect on the quality characteristics of sperm was reversible.

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

Pregnancy

No teratogenic or selective embryotoxic activity of paroxetine was detected in animal studies.

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

When prescribing paroxetine, the doctor should consider the possibility of alternative treatment for pregnant women and women planning pregnancy. Paroxetine should only be prescribed if its potential benefit outweighs the potential risk. If a decision is made to discontinue treatment with paroxetine during pregnancy, the doctor should follow the recommendations of the sections “Dosage and use” (“Withdrawal of paroxetine”) and “Special instructions” (“Symptoms observed when stopping treatment with paroxetine in adults”).

Preterm birth has been reported in women who received paroxetine or other SSRI medications during pregnancy, but a causal relationship between these medications and preterm birth has not been established.

It is necessary to monitor the health status 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 SSRI drugs in the third trimester of pregnancy. However, the causal relationship between these complications and this drug therapy has not been confirmed. The clinical complications described included: respiratory distress syndrome, cyanosis, apnea, convulsive seizures, temperature instability, difficulty feeding, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, increased neuro-reflex excitability syndrome, irritability, lethargy, constant crying and drowsiness. In some reports, the symptoms were described as neonatal manifestations of withdrawal syndrome. In most cases, the described complications occurred immediately after delivery or shortly after it ( According to epidemiological studies, taking SSRIs (including paroxetine) during pregnancy, in particular in the late stages, 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 is 4-5 times higher than that observed in the general population (1-2 per 1000 pregnancies).

The results of animal studies indicate reproductive toxicity of the drug, but no direct adverse effects on pregnancy, embryo and fetal development, childbirth or postnatal development have been established.

Breast-feeding period

A small amount of paroxetine penetrates into breast milk. In published studies in breastfed infants, the serum concentration of paroxetine was undetectable (<2 ng / ml) or very low (

In children, no signs of exposure to the drug were detected. However, paroxetine should not be taken during breastfeeding unless its benefits to the mother outweigh the potential risks to the baby.

Contraindications

• Hypersensitivity to paroxetine and any other component of the drug;
• Paroxetine is contraindicated in combination with monoamine oxidase inhibitors (MAOIs). In exceptional cases, linezolid (an antibiotic that is a reversible non-selective MAOI) can be combined with paroxetine, provided that acceptable alternatives to treatment with linezolid are not available, and the potential benefits of linezolid use outweigh the risks of serotonin syndrome or neuroleptic malignant syndrome, as a reaction in a particular patient.

Equipment should be available to closely monitor serotonin syndrome symptoms and monitor blood pressure.

Treatment with paroxetine is allowed:

• 2 weeks after discontinuation of treatment with irreversible MAOIs;
• at least 24 hours after discontinuation of treatment with reversible MAOIs (for example, moclobemide, linezolid, methylthioninium chloride (methylene blue)),
• at least 1 week should elapse between the withdrawal of paroxetine and the start of therapy with any MAOIs.
• Paroxetine is contraindicated for use in combination with thioridazine, since, like other drugs that inhibit the activity of the hepatic isoenzyme CYP450 2D6, paroxetine can increase the concentration of thioridazine in blood plasma. The use of thioridazine can lead to prolongation of the QTc interval and the development of torsades de pointes ventricular tachycardia associated with this phenomenon and sudden death;
• Paroxetine is contraindicated in combination with pimozide.

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

Side effects

The frequency and intensity of some of the following adverse reactions to paroxetine may decrease with continued treatment, and such reactions usually do not require discontinuation of the drug. The adverse reactions listed below are listed according to organ system involvement and frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare ( The incidence of frequent and infrequent adverse reactions was determined based on generalized data on the safety of the drug in more than 8000 patients who participated in clinical trials, the indicator was calculated by the difference between the frequency of adverse reactions in the paroxetine group and in the placebo group. The occurrence of rare and very rare adverse reactions was determined based on post-marketing data, and this indicator reflects more the frequency of reports of such reactions than the true frequency of reactions.

Frequency of adverse reactions

Disorders of the blood and lymphatic system:

infrequently-pathological bleeding, mainly hemorrhage in the skin and mucous membranes (including ecchymosis);

very rarely – thrombocytopenia.

Immune system disorders:

very rarely – severe allergic reactions (including anaphylactoid reactions and angioedema).

Endocrine system disorders:

very rarely – syndrome of inadequate secretion of antidiuretic hormone.

Metabolic and nutritional disorders:

often-decreased appetite, increased cholesterol concentration;

rarely-hyponatremia.

Hyponatremia occurs mainly in elderly patients and in some cases is caused by the syndrome of inadequate secretion of antidiuretic hormone.

Mental disorders:

often – drowsiness, insomnia, agitation, abnormal 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 discontinuation of treatment. These symptoms may be due to an underlying medical condition.

Nervous system disorders:

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 tremors and tremor).

Extrapyramidal symptoms, including orofacial dystonia, have sometimes been observed in patients with impaired motor functions or who have used neuroleptics.

Visual disturbances:

often – blurred vision;

infrequently-mydriasis;

very rarely-acute glaucoma.

Hearing and balance disorders:

frequency unknown-tinnitus.

Disorders of the cardiovascular system:

infrequently – sinus tachycardia, postural hypotension, temporary increase or decrease in blood pressure.

Temporary increases and decreases in blood pressure have been reported after paroxetine treatment, usually in patients with prior hypertension or anxiety;

rarely, bradycardia.

Respiratory, thoracic and mediastinal disorders:

often – yawning.

Disorders of the gastrointestinal tract:

very often – nausea;

often-constipation, diarrhea, vomiting, dry mouth;

very rarely-gastrointestinal bleeding.

Liver and biliary tract disorders:

rarely-increased activity of liver enzymes;

very rarely-adverse reactions from the liver (such as hepatitis, sometimes accompanied by jaundice and / or liver failure).

Increased liver enzyme activity 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 whether to discontinue treatment with paroxetine should be addressed in cases where there is a long-term increase in liver function tests.

Skin and subcutaneous tissue disorders:

often – increased sweating,

infrequently-skin rashes, pruritus;

very rarely-photosensitivity reactions, severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), urticaria.

Renal and urinary tractdisorders:

infrequently-urinary retention, urinary incontinence.

Disorders of the genitals and mammary glands:

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 conducted mainly in patients aged 50 years and older have shown an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism underlying this risk is unknown.

General disorders and disorders at the injectionsite:

often-asthenia, weight gain;

very rarely-peripheral edema.

Symptoms that occur when paroxetine treatment is discontinued:

often – dizziness, sensory disturbances, sleep disturbances, anxiety, headache;

infrequently-agitation, nausea, tremor, confusion, increased sweating, emotional lability, visual disturbances, palpitation, diarrhea, irritability.

As with the withdrawal of other psychotropic medications, discontinuation of paroxetine treatment (especially abrupt) 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, palpitation, emotional lability, irritability, visual disturbances. In most patients, these symptoms are mild to moderate and resolve spontaneously. No group of patients is known to be at an increased risk of such symptoms; therefore, if treatment with paroxetine is no longer necessary, the dose should be reduced slowly until the drug is completely discontinued.

Adverse reactions observed in clinical trials involving children

The following adverse reactions were observed in clinical trials involving children: 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 involving adolescents with moderate to severe depressive episodes and recurrent depressive disorder. Hostility was observed in particular in children with obsessive-compulsive disorder, especially in children under 12 years of age.

In clinical studies, when the daily dose was gradually reduced (the daily dose was reduced by 10 mg per day at intervals of one week to a dose of 10 mg per 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 with a reduction in the dose of paroxetine or after complete discontinuation of the drug

Interaction

Serotonergic drugs

The use of paroxetine, as well as other SSRI drugs, simultaneously with serotonergic drugs can cause effects associated with 5-HT receptors (serotonin syndrome). Caution and careful clinical monitoring should be observed when concomitant use of serotonergic drugs (including L-tryptophan, tryptane preparations, tramadol, SSRI preparations, fentanyl, lithium, and St. John’s wort preparations) with paroxetine is necessary.

Concomitant use of paroxetine with MAO inhibitors (including linezolid (an antibiotic that is a reversible non-selective MAO inhibitor) and methylthioninium chloride (methylene blue) is contraindicated.

Pimozide

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

Enzymes involved in drug metabolism

The metabolism and pharmacokinetics of paroxetine may change under the influence of induction or inhibition of enzymes involved in drug metabolism.

When using paroxetine simultaneously with a known inhibitor of enzymes involved in drug metabolism, the use of paroxetine at a dose that is at the lower end of the therapeutic dose range should be recommended.

The initial dose of paroxetine is not adjusted if it is used simultaneously with a drug that is a known inducer of enzymes involved in drug metabolism (for example, carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent dose adjustment of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Fosamprenavir and ritonavir

Co-use 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 comparable to control values from other studies, which indicates that there is no significant effect of paroxetine on the metabolism of fosamprenavir/ritonavir. There are no data on the effect of long-term co-use of paroxetine with fosamprenavir/ritonavir. Any 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.

Anticonvulsant medications

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

Muscle relaxants

Drugs of the group of selective serotonin reuptake inhibitors (SSRIs) 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 SSRIs, paroxetine inhibits the liver enzyme CYP2D6, which belongs to the cytochrome P450 system. Inhibition of the CYP2D6 enzyme can lead to an increase in plasma concentrations of concomitantly used drugs that are metabolized by this enzyme. These medications include certain tricyclic antidepressants (such as amitriptyline, nortriptyline, imipramine, and desipramine), phenothiazine-type neuroleptics (perphenazine and thioridazine), risperidone, atomoxetine, certain Class 1 c antiarrhythmic drugs (such as propafenone and flecainide), and metoprolol. It is not recommended to use paroxetine in combination with metoprolol in heart failure, due to the narrow therapeutic index of metoprolol with this indication for use.

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

SURAH 3 A 4

An in vivo interaction study evaluating the concomitant use of paroxetine and terfenadine, which is a substrate of the CYP3A4 isoenzyme, showed that paroxetine does not affect the pharmacokinetics of terfenadine. A similar in vivo interaction study found no effect of paroxetine on the pharmacokinetics of alprazolam, and vice versa. Concomitant use of paroxetine with terfenadine, alprazolam and other drugs that are a substrate of the CYP3A4 isoenzyme is not expected to have a negative effect on the patient.

Drugs that affect the pH of the stomach

In clinical studies, it is shown that the absorption and pharmacokinetics of paroxetine are independent or almost independent (i. e. existing dependency does not require modification of the dose) from:

• meals,
• antacids,
• digoxin,
• propranolol,
• alcohol paroxetine does not increase the negative impact of alcohol on mental and motor function, however, it is also not recommended to take paroxetine and alcohol.

Oral anticoagulants

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

Nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid and other antiplatelet drugs

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

Caution should be exercised in the treatment of patients receiving SSRIs concomitantly with oral anticoagulants, with 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, cyclooxygenase-2(COX – 2) inhibitors), as well as in the treatment of patients with a history of clotting disorders blood loss or conditions that may cause a predisposition to bleeding.

How to take, course of use and dosage

The drug Paroxetine-SZ is recommended to be taken 1 time a day in the morning with meals. Tablets should be swallowed without chewing. The applied formula allows you to divide the tablet in half if necessary to get a dose of 10 mg.

• Moderate to severe depressive episodes and recurrent depressive disorder

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

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

• Obsessive-compulsive disorder (OCD)

The recommended dose is 40 mg per day. Treatment of patients should begin 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 a maximum dose of 60 mg per day.

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

• Panic disorder

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

A low initial dose is recommended to minimize the possible increase in symptoms of panic disorder that may occur at the beginning of treatment for this disorder.

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

• Social phobia

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

• Generalized anxiety disorder

The recommended dose is 20 mg per day. If necessary, the dose can be increased in increments of 10 mg per day to a maximum dose of 50 mg per day, depending on the clinical response.

• Post-traumatic stress disorder

The recommended dose is 20 mg per day. If necessary, the dose can be increased in increments of 10 mg to a maximum dose of 50 mg per day, depending on the clinical response.

General information

Withdrawal of paroxetine.

As with other psychotropic medications, abrupt withdrawal of Paroxetine-SZ should be avoided.

The scheme of gradual dose reduction used in recent clinical studies was to reduce the daily dose by 10 mg per week. After reaching the dose of 20 mg per day, patients continued to take this dose for 1 week, and only after that the drug was completely discontinued. If withdrawal symptoms develop during dose reduction or after discontinuation of the drug, it is advisable to resume taking the previously prescribed dose. In the future, the doctor may continue to reduce the dose, but more slowly.

Special patient groups

Elderly patients

In elderly patients, the concentration of paroxetine in the blood plasma may increase, but the range of its concentrations in the blood plasma coincides with that in younger patients.

In this category of patients, therapy should begin with the recommended dose for adults, which can be increased to 40 mg per day.

Patients with impaired renal or hepatic function

The concentration of paroxetine in blood plasma increases in patients with severe renal impairment (creatinine clearance less than 30 ml / min) and in patients with impaired liver function. Therefore, such patients should be prescribed doses of the drug that are at the lower end of the therapeutic dose range.

Children and adolescents (under 18 years of age)

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

Overdose

Symptoms

The available information about paroxetine overdose indicates its wide range of safety.

In case of an overdose of paroxetine, in addition to the symptoms described in the section “Side effects”, fever, changes in blood pressure, involuntary muscle contractions, anxiety and tachycardia are observed.

Patients ‘ condition 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, and fatal outcomes were very rare, usually reported in situations where patients took paroxetine together with other psychotropic drugs with or without alcohol.

Treatment

The specific antidote of paroxetine is unknown. Treatment should include general measures used for overdose of any antidepressants. Maintenance therapy and frequent monitoring of the main physiological parameters, as well as careful monitoring, are indicated. Treatment of the patient should be carried out in accordance with the clinical picture or in accordance with the recommendations of the national toxicology center, if any.

Description

Tablets covered with a film-coated white or almost white color, round, biconvex with a risk on one side. On a cross-section, the tablet core is white or almost white in color.

Special instructions

Children and adolescents (under 18 years of age)

Paroxetine-SZ should not be used in children and adolescents under 18 years of age.

Treatment with antidepressants in children and adolescents with moderate to severe depressive episodes, recurrent depressive disorder, and other mental illnesses is associated with an increased risk of suicidal thoughts and behavior.

In clinical studies, adverse reactions associated with suicidal attempts and suicidal thoughts, hostility (mainly aggression, deviant behavior, and anger) were more common in children and adolescents treated with paroxetine than in patients in this age group who received placebo. Currently, there are no data on the long-term safety of paroxetine for children and adolescents, which would relate to the effect of this drug on growth, maturation, cognitive and behavioral development.

Clinical deterioration and suicidal risk in adults

Young patients, especially those with moderate to severe depressive episodes and recurrent depressive disorder, may be at an increased risk of suicidal behavior during paroxetine therapy. An analysis of placebo-controlled studies in adults with mental illnesses indicates an increase in the frequency of suicidal behavior in young patients (at a prospectively determined age of 18-24 years) while taking paroxetine compared to the placebo group: 17/776 (2.19%) vs. 5/542 (0.92%), respectively, although the observed difference was not statistically significant. No increase in the frequency of suicidal behavior was observed in patients of older age groups (from 25 to 64 years and older than 65 years). In adults of all age groups with moderate and severe depressive episodes and recurrent depressive disorder, there was a statistically significant increase in the number of suicidal behavior cases during paroxetine treatment compared to the placebo group (suicide attempt rate: 11/3455 (0.32%) vs. 1/1978 (0.05%), respectively). However, most of these paroxetine-related cases (8 out of 11) were reported in young patients aged 18 to 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 over 24 years of age with various mental disorders.

In patients with depression, an increase in symptoms and / or the appearance of suicidal thoughts and behavior (suicidality) may occur regardless of the use of antidepressants. This risk persists until a pronounced remission is achieved. Overall, clinical experience with all antidepressants suggests 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, and 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 most at risk of suicidal thoughts or attempts. All patients should be 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 changes in the dose of the drug (increase or decrease).

Patients (and their caregivers) should be warned to monitor their condition for deterioration (including the development of new symptoms) and/or the appearance of suicidal behavior or thoughts of self-harm. If these symptoms occur, you should seek immediate medical attention.

It should be remembered that symptoms such as agitation, akathisia or mania may be associated with the underlying disease or 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 suddenly appear, increase in severity of manifestations, or if the symptoms were not part of the previous symptom complex in this patient, it is necessary to reconsider the therapy regimen until discontinuation of the drug.

Akathisia

In rare cases, treatment with paroxetine or other SSRI drugs is accompanied by the development of akathisia, which is manifested by a feeling of internal anxiety and psychomotor agitation, when the patient cannot sit or stand still; with akathisia, the patient usually experiences subjective discomfort.

Akathisia is most likely to occur in the first few weeks of treatment.

Serotonin syndrome, neuroleptic malignant syndrome

In rare cases, serotonin syndrome or symptoms similar to neuroleptic malignant syndrome may develop during treatment with paroxetine, in particular if paroxetine is used in combination with other serotonergic drugs and/or neuroleptics. These syndromes are potentially life-threatening, 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, irritability, extremely severe agitation, progressing to delirium and coma), and supportive symptomatic therapy should be initiated. Paroxetine should not be used in combination with serotonin precursors (such as L-tryptophan, oxy-triptan) 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. Prior to starting treatment with an antidepressant, a thorough screening should be conducted to assess the patient’s risk of bipolar disorder; such screening should include collecting a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not intended for the treatment of a depressive episode within bipolar disorder. Like other antidepressants, paroxetine should be used with caution in patients with a history of mania.

Tamoxifen

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

Bone fractures

Epidemiological studies evaluating the risk of bone fractures have linked bone fractures to the use of certain antidepressants, including SSRIs. The risk was observed during the course of treatment with antidepressants and was maximal at the beginning of the course of therapy. The likelihood of bone fractures should be considered when using paroxetine.

Diabetes mellitus

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

IMAO

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

Caution is recommended when using paroxetine in patients with severe renal impairment or patients with impaired liver function.

Epilepsy

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

Convulsive seizures

The frequency of convulsive 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 concomitant use of paroxetine and electroconvulsive therapy.

Glaucoma

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

Hyponatremia

Hyponatremia is rare in patients treated with paroxetine, is observed mainly in elderly patients and is leveled after paroxetine withdrawal.

Bleeding issues

Skin and mucosal hemorrhages (including gastrointestinal and gynecological bleeding) have been reported in patients receiving paroxetine. Therefore, paroxetine should be used with caution in patients who are receiving concomitant medications that increase the risk of bleeding, in patients with a known tendency to bleed, and in patients with diseases predisposing to bleeding.

Heart disease

The usual precautions should be taken when treating patients with heart disease.

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 addictive or addictive, as is the case with substances that are the subject of abuse.

Withdrawal symptoms are described as dizziness, sensory disturbances (including paresthesia, electric shock and tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, tremor, confusion, increased sweating, headaches and diarrhea, palpitations, emotional lability, irritability and visual disturbances. These symptoms are usually mild to moderate, but may be severe in some patients. These symptoms are usually mild to moderate, but may be severe in some patients. 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. Usually, 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 its complete withdrawal, depending on the needs of the individual patient.

Symptoms that may occur when paroxetine treatment 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%. After paroxetine withdrawal, the following adverse reactions were reported 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.

Influence on the ability to drive vehicles and mechanisms

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

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.

Form of production

Film-coated tablets,20 mg.

10 or 14 tablets in a cell contour package.

30 tablets each in a low-pressure polyethylene polymer jar with a high-pressure polyethylene lid or in a low-pressure polyethylene polymer bottle with a high-pressure polyethylene lid.

Each jar, bottle,3,5 packs of cell contour 10 tablets or 2,4 packs of cell contour 14 tablets together with the instructions for use are placed in a cardboard pack.

Storage conditions

In a place protected from light, at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Paroxetine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets