Paroxetine-SZ, 20 mg 30 pcs

Pharmacotherapeutic group: antidepressant.

ATX code: N06AB05

Pharmacological properties

Pharmacodynamics

Mechanism of action

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

Paroxetine differs chemically from tricyclic, tetracyclic and other known antidepressants.

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

In keeping with this selective action of paroxetine, studies in vitro it has been shown that, unlike tricyclic antidepressants, it has little affinity for α-1, α-2, and β-adrenoreceptors, as well as for dopamine (D₂), 5-NT₁-like, 5-NT₂– and histamine (H₁) receptors. The lack of interaction with postsynaptic receptors in vitro is confirmed by studies in vivo, which indicate that paroxetine does not depress the central nervous system (CNS) and does not cause arterial hypotension.

Pharmacodynamic properties

Paroxetine does not impair psychomotor function or increase the CNS depressant effect of ethanol.

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

In behavioral and EEG assessment studies, paroxetine has been shown to cause weak activating effects at doses greater than those required to inhibit 5-NT reuptake. Its activating properties are not “amphetamine-like” in nature.

In animal studies, good cardiovascular tolerance has been shown.

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

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

Pharmacokinetics

Intake

Paroxetine is well absorbed after oral administration and undergoes first-pass metabolism.

Due to first-pass metabolism, a smaller amount of paroxetine enters the systemic bloodstream than is absorbed from the gastrointestinal tract. As the amount of paroxetine in the body increases with a single high-dose administration or with multiple conventional doses, there is partial saturation of the first-pass metabolic pathway and a decrease in the clearance of paroxetine from the blood plasma. This results in a disproportionate increase in plasma concentrations of paroxetine, so its pharmacokinetic parameters are inconsistent, resulting in nonlinear kinetics. However, the non-linearity of kinetics is usually insignificant and is observed only in those patients in whom low paroxetine plasma concentrations are achieved at low doses of the drug.

The equilibrium systemic concentrations are reached 7-14 days after initiation of paroxetine treatment, its pharmacokinetic parameters generally do not change during long-term therapy.

Distribution

Paroxetine is widely distributed in tissues, and pharmacokinetic calculations indicate that only 1% of the total amount of paroxetine present in the body remains in plasma.

In therapeutic concentrations, approximately 95% of the plasma paroxetine present is bound to proteins.

No correlation has been found between the plasma concentration of paroxetine and its clinical effects (with adverse reactions and efficacy).

Metabolism

The main metabolites of paroxetine are polar and conjugated oxidation and methylation products that are readily 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 act on 5-NT reuptake in neurons.

Elimation

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

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

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

Special patient groups

Elderly patients, patients with renal or hepatic impairment.

In elderly patients, patients with severe renal or hepatic impairment, plasma concentrations of paroxetine may increase, but the range of its plasma concentrations is the same as in healthy adults.

Indications

The results of studies in which patients have taken paroxetine for up to
1 year show that it is effective in preventing relapses and return of symptoms. Results from studies in which patients have taken paroxetine for up to
1 year suggest that it is effective in preventing relapses and the return of depression symptoms.

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

The efficacy of paroxetine in treating OCD has been maintained for at least 1 year, according to placebo-controlled studies. In addition, paroxetine is effective in preventing relapses of OCD.

Paroxetine is effective in treating panic disorder with and without agoraphobia, including as maintenance and preventive therapy.

The combination of paroxetine and cognitive behavioral therapy has been found to be significantly more effective in the treatment of panic disorder than the isolated use of cognitive behavioral therapy.

The efficacy of paroxetine in treating panic disorder was maintained for more than 1 year according to placebo-controlled studies. In addition, paroxetine was effective in preventing relapses of panic disorder.

Paroxetine is effective in treating social phobia, including as long-term maintenance and preventive therapy.

The continued effectiveness 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, including as long-term maintenance and preventive 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 treating post-traumatic stress disorder

Active ingredient

Composition

1 film-coated tablet contains:

the active substance:

paroxetine hydrochloride hemic hydrate – 22.8 mg, in terms of paroxetine – 20 mg;

auxiliary substances (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;

Ancillary substances (coating): Hypromellose, 4.59 mg; polysorbate-80 (tween-80), 1.91 mg; talc, 1.53 mg; titanium dioxide E 171, 0.97 mg.

How to take, the dosage

The drug Paroxetine-SZ is recommended to be taken once a day in the morning with a meal. The tablets should be swallowed without chewing. The applied risk allows dividing the tablet in half to obtain a dose of 10 mg, if necessary.

The recommended dose is 20 mg daily. If necessary, the dose may be increased in increments of 10 mg per day to a maximum dose of
50 mg per day, depending on clinical response. As with any antidepressant treatment, the efficacy 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 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.

The recommended dose is 40 mg per day. Patients should begin treatment 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 state. This period may be several months.

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

The low starting dose is recommended to minimize the possible increase in panic disorder symptomatology 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 state. This period may be several months or longer.

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

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

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

General Information

Paroxetine withdrawal.

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

The gradual dose reduction scheme used in recent clinical trials was to reduce the daily dose by 10 mg per week. After reaching a dose of 20 mg per day, patients continued taking this dose for 1 week, and only then was the drug withdrawn completely. If withdrawal symptoms develop during dose reduction or after withdrawal of the drug, it is advisable to resume the previously prescribed dose. The physician may continue to reduce the dose at a slower rate thereafter.

Special patient groups

Elderly patients

In elderly patients, plasma concentrations of paroxetine may increase, but the range of plasma concentrations is the same as in younger patients.

In this category of patients, therapy should be started at the dose recommended for adults, which may be increased to 40 mg daily.

Patients with renal or hepatic impairment

The plasma concentration of paroxetine is increased 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 limit of the therapeutic dose range.

Children and adolescents (younger than 18 years)

The use of paroxetine in children and adolescents (younger than 18 years) is contraindicated.

Interaction

Serotonergic drugs

The use of paroxetine, as well as other drugs of the SSRI group, simultaneously with serotonergic drugs may cause effects associated with 5-NT receptors (serotonin syndrome). Caution and close clinical monitoring are required when concomitant use of serotonergic drugs (including
L-tryptophan, tryptans, tramadol, SSRIs, fentanyl, lithium and St. John’s wort preparations) with paroxetine.

The concomitant use of paroxetine with MAOI inhibitors (including linezolid (an antibiotic that is a reversible non-selective MAOI inhibitor) and methylthionine chloride (methylene blue) is contraindicated.

Pimozide

In a study of concomitant use of paroxetine and pimozide in a single low dose (2 mg), an increased concentration of pimozide was reported. This fact is explained by the 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, concomitant use of pimozide and paroxetine is contraindicated.

The enzymes involved in drug metabolism

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

When using paroxetine concomitantly with a known inhibitor of enzymes involved in drug metabolism, 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 (e.g., carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent dose adjustment of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Fosamprenavir and ritonavir

The co-administration of fosamprenavir/ritonavir with paroxetine resulted in a significant decrease in plasma paroxetine concentrations. Plasma concentrations of fosamprenavir/ritonavir when concomitantly used with paroxetine were comparable to control values from other studies, indicating no significant effect of paroxetine on fosamprenavir/ritonavir metabolism. There are no data on the effects of long-term co-administration of paroxetine with fosamprenavir/ritonavir. Any dose adjustment of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Procyclidine

Daily administration of paroxetine significantly increases plasma concentrations of procyclidine. If anticholinergic effects occur, the dose of procyclidine should be reduced.

Convulsants

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

Myorelaxants

The drugs of the group of selective serotonin reuptake inhibitors (SSRIs) may decrease plasma cholinesterase activity, which leads to an increase in the duration of neuromuscular blocking effects of mivacurium and suxamethonium.

Paroxetine’s ability to inhibit the CYP2D6 isoenzyme

Like other antidepressants, including other drugs in the SSRI group, paroxetine inhibits the hepatic CYP2D6 enzyme belonging to the cytochrome P450 system. Inhibition of CYP2D6 enzyme may lead to increased plasma concentrations of simultaneously used drugs that are metabolized by this enzyme. Such drugs include some tricyclic antidepressants (e.g., amitriptyline, nortriptyline, imipramine and desipramine), phenothiazine-type neuroleptics (perphenazine and thioridazine), risperidone, atomoxetine, some class 1c antiarrhythmic agents (such as propafenone and flecainide) and metoprolol. Paroxetine is not recommended in combination with metoprolol for heart failure, due to the narrow therapeutic index of metoprolol in this indication.

The irreversible inhibition of the CYP2D6 system by paroxetine may lead to decreased plasma concentrations of endoxifen and decreased effectiveness of tamoxifen.

CYP3A4

An in vivo study to evaluate the interaction when used concomitantly under equilibrium conditions of paroxetine and terfenadine, which is a substrate of 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 substrates of CYP3A4 isoenzyme is not expected to have adverse effects on the patient.

Drugs that affect gastric pH

The absorption and pharmacokinetics of paroxetine have been shown in clinical studies to be independent or virtually independent (i.e. existing dependence does not require a change in dose) on:

Peroral anticoagulants

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

Non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid and other antiplatelet agents

Possible 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 when treating patients receiving SSRIs concomitantly with oral anticoagulants, with drugs that affect platelet function or increase the risk of bleeding (e.g., atypical neuroleptics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, NSAIDs, cyclooxygenase-2 inhibitors

Special Instructions

Children and adolescents (younger than 18 years)

The drug Paroxetine-SZ should not be used in children and adolescents younger than
18 years.

The treatment with antidepressants in children and adolescents with moderate to severe depressive episodes, recurrent depressive disorder and other mental illnesses is accompanied by an increased risk of suicidal ideation and suicidal behavior.

In clinical studies, adverse reactions associated with suicide attempts and suicidal ideation and hostility (primarily aggression, deviant behavior and anger) were observed more frequently in children and adolescents who received paroxetine than in patients in this age group who received placebo. There are currently no data on the long-term safety of paroxetine in children and adolescents that address the drug’s effects on growth, maturation, cognitive and behavioral development.

Clinical impairment and suicidal risk in adults

Younger patients, especially those with moderate to severe depressive episodes and recurrent depressive disorder, may be at increased risk for suicidal behavior during paroxetine therapy. An analysis of placebo-controlled studies in adults with mental illness indicates an increased incidence of suicidal behavior in younger patients (prospectively defined age 18-24 years) on paroxetine compared to the placebo group: 17/776 (2.19%) versus 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 in older age groups
(25 to 64 years and over 65 years). In adults of all age groups with moderate to severe depressive episodes and recurrent depressive disorder, there was a statistically significant increase in suicidal behavior during treatment with paroxetine compared to the placebo group (frequency of suicide attempts: 11/3455 (0.32%) vs 1/1978 (0.05%), respectively). However, the majority of these cases on paroxetine (8 of 11) were in young patients between the ages of 18 and 30. Data from a study involving patients with moderate to severe depressive episodes and recurrent depressive disorder may indicate an increased incidence of suicidal behavior in younger patients, which may persist in patients over 24 years of age with various psychiatric disorders.

In depressed patients, exacerbation of symptoms and/or the occurrence of suicidal ideation and suicidal behavior (suicidality) may be observed regardless of receiving antidepressants. This risk persists until significant remission is achieved. In general, clinical experience with all antidepressants shows 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 combined with moderate to severe depressive episodes and recurrent depressive disorder. In addition, patients with a history of suicidal behavior or suicidal ideation, younger patients, and patients with significant suicidal ideation prior to treatment are at greatest risk for suicidal thoughts or attempts. All patients should be monitored for timely detection of clinical deterioration (including new symptoms) and suicidality throughout treatment, especially at the beginning of treatment, or during dose changes (increases or decreases).

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

It is important to remember that symptoms such as agitation, akathisia or mania may be related to either the underlying illness or a consequence of the therapy used.

If symptoms of clinical deterioration (including the development of new symptoms) and/or suicidal ideation and/or suicidal behavior occur, particularly if they appear suddenly, if their severity increases, or if the symptoms were not part of a previous symptom presentation in this patient, the therapy should be reviewed until the drug is discontinued.

Akathisia

In rare cases, treatment with paroxetine or another SSRI product is accompanied by akathisia, which is a feeling of inner restlessness and psychomotor agitation in which the patient cannot sit or stand quietly; the patient usually feels subjective discomfort.

The likelihood of akathisia is highest in the first few weeks of treatment.

Serotonin syndrome, malignant neuroleptic syndrome

In rare cases, serotonin syndrome or symptoms similar to malignant neuroleptic syndrome may develop with paroxetine treatment, particularly if paroxetine is used in combination with other serotonergic drugs and/or neuroleptics. These syndromes are potentially life-threatening, and therefore paroxetine treatment should be discontinued if they occur (they are characterized by groups of symptoms such as hyperthermia, muscle rigidity, myoclonus, autonomic disturbances with possible rapid changes in vital signs, mental status changes including confusion, irritability, extremely severe agitation, progressing to delirium and coma) and symptomatic maintenance therapy should be started. Paroxetine should not be used in combination with serotonin precursors (such as L-tryptophan, oxytriptan) because of the risk of serotoninergic syndrome.

Mania and bipolar disorder

A major depressive episode may be the initial manifestation of bipolar disorder. It is generally believed (although not proven by controlled clinical trials) that treatment of such an episode with an antidepressant alone may increase the likelihood of accelerated development of a mixed or manic episode in patients at risk for bipolar disorder. Before starting antidepressant treatment, a thorough screening should be performed to assess the patient’s risk of bipolar disorder; such a screening should include a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not intended to treat 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 efficacy of tamoxifen, assessed by the risk of breast cancer recurrence and mortality, may be reduced when used together with paroxetine due to the irreversible inhibition of the CYP2D6 isoenzyme by paroxetine. The risk may increase with prolonged co-administration. When using tamoxifen to treat or prevent breast cancer, consider using alternative antidepressants that do not inhibit the CYP2D6 isoenzyme or have a lesser effect.

Bone fractures

Epidemiological studies assessing the risk of bone fractures have found an association of bone fractures with taking certain antidepressants, including SSRIs. The risk was observed during the course of antidepressant treatment and was maximal at the beginning of therapy. The likelihood of bone fractures should be considered when using paroxetine.

Diabetes

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

IMAOs

Paroxetine treatment should be started with caution 2 weeks after stopping treatment with irreversible IMAOs or 24 hours after stopping treatment with reversible IMAOs. The dose of paroxetine should be increased gradually until optimal therapeutic effect has been achieved.

Recautions are 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 incidence 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 concomitant use of paroxetine and electroconvulsive therapy.

Glaucoma

Like other drugs in the SSRI group, paroxetine may cause mydriasis and should be used with caution in patients with closed-angle glaucoma.

Hyponatremia

Paroxetine treatment rarely causes hyponatremia, occurs mostly in elderly patients, and levels out after paroxetine withdrawal.

Bleeding

Bleeding of the skin and mucous membranes (including gastrointestinal and gynecological bleeding) has been reported in patients while taking paroxetine. Therefore, paroxetine should be used with caution in patients who simultaneously receive drugs that increase the risk of bleeding, in patients with a known propensity for bleeding, and in patients with conditions that predispose to bleeding.

Heart disease

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

The symptoms observed when continuing paroxetine treatment in adults

The symptoms withheld 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%, whereas the incidence of adverse reactions in the placebo group was 20%. Withdrawal symptoms did not imply addiction or dependence, as with substances of abuse.

Symptoms of withdrawal have been described as dizziness, sensory disturbances (including paresthesias, electric shocks and tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, tremors, 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. Usually these symptoms are mild to moderate, but in some patients they may be severe. Symptoms usually develop in the first few days after withdrawal of the drug, but in very rare cases occur in patients who have accidentally missed a dose. These symptoms usually go away spontaneously and disappear within 2 weeks, but some patients may have symptoms for much longer (2-3 months or more). It is recommended that the dose of paroxetine be reduced gradually over a period of weeks or months before withdrawing it completely, depending on the needs of the individual patient.

Symptoms that may occur when discontinuing paroxetine treatment in children and adolescents.

In clinical studies in children and adolescents, the incidence of adverse reactions when paroxetine was withdrawn was 32%, whereas 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 twice as often as in the placebo group: emotional lability (including suicidal thoughts, suicide attempts, mood changes and tearfulness), nervousness, dizziness, nausea and abdominal pain.

Influence on ability to drive vehicles, mechanisms

Clinical experience with paroxetine indicates that it does not impair cognitive or psychomotor function. However, as with any other psychotropic medication, patients should be especially careful when driving and operating machinery.

While paroxetine does not increase the negative effects of alcohol on psychomotor functions, it is not recommended to use paroxetine and alcohol concomitantly.

Synopsis

Contraindications

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

Paroxetine treatment is allowed:

Side effects

The frequency and intensity of some of the paroxetine adverse reactions listed below may decrease as treatment continues, and such reactions usually do not require withdrawal of the drug. The adverse reactions presented below are listed according to organ system involvement and frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), frequent (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), rare (≥1/10000, < 1/1000), very rare (< 1/10000), including individual cases, and frequency unknown. The incidence of frequent and infrequent adverse reactions was determined based on summarized safety data from more than 8,000 patients participating in clinical trials, calculated from the difference between the incidence of adverse reactions in the paroxetine group and in the placebo group. The incidence of rare and very rare adverse reactions was determined based on post-marketing data, and this rate reflects the frequency of reported reactions more than the true incidence of reactions.

Frequency of adverse reactions

Blood and lymphatic disorders:

infrequent – pathological bleeding, mainly bleeding in the skin and mucous membranes (including ecchymosis);

very rare – thrombocytopenia.

Disorders with the immune system:

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

Disorders of the endocrine system:

very rare – syndrome of inadequate secretion of antidiuretic hormone.

Disorders of metabolism and nutrition:

often – decreased appetite, increased cholesterol concentration;

rarely – hyponatremia.

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

Psychiatric disorders:

often – somnolence, insomnia, agitation, abnormal dreams (including nightmares);

infrequently – confusion, hallucinations;

rarely – manic reactions, anxiety, depersonalization, panic attacks, akathisia;

frequency unknown – suicidal thoughts and suicidal behavior.

Incidents of suicidal ideation 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 – seizures, restless legs syndrome;

very rarely – serotonin syndrome (symptoms may include agitation, confusion, increased sweating, hallucinations, hyperreflexia, myoclonus, tachycardia with tremors, and tremors).

The development of extrapyramidal symptoms, including orofacial dystonia, has sometimes been observed in patients with motor dysfunction or who have used neuroleptics.

Visual disturbances:

often – blurred vision;

infrequently – mydriasis;

very rarely – acute glaucoma.

Hearing organ and balance disorders:

frequency unknown – tinnitus.

Disorders on the side of the cardiovascular system:

infrequent – sinus tachycardia, postural hypotension, temporary increase and decrease in blood pressure.

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

rarely, bradycardia.

Disorders of the respiratory system, chest and mediastinum:

frequent – yawning.

Gastrointestinal disorders:

very often – nausea;

often – constipation, diarrhea, vomiting, dry mouth;

very rarely – gastrointestinal bleeding.

Hepatic and biliary tract disorders:

rarely – increased liver enzyme activity;

very rare – adverse reactions in the liver (such as hepatitis, sometimes accompanied by jaundice and/or liver failure).

Elevated hepatic enzyme activity has been reported. Post-registration reports of adverse liver reactions (such as hepatitis, sometimes accompanied by jaundice and/or liver failure) have been very rarely observed. The appropriateness of discontinuing treatment with paroxetine should be considered in cases of prolonged increase in liver function tests.

Dermal and subcutaneous tissue disorders:

often – increased sweating,

infrequent – skin rash, itching;

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

Kidney and urinary tract disorders:

infrequent – urinary retention, urinary incontinence.

Disorders of the genitals and mammary glands:

very common – sexual dysfunction;

rarely – hyperprolactinemia, galactorrhea, menstrual cycle disorders (including menorrhagia, metrorrhagia and amenorrhea);

very rare – priapism.

Musculoskeletal disorders:

rarely – arthralgia, myalgia.

Epidemiological studies, conducted primarily with 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 site of administration:

often, asthenia, weight gain;

very rarely, peripheral edema.

Symptoms occurring on discontinuation of paroxetine treatment:

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

infrequently – agitation, nausea, tremor, confusion, increased sweating, emotional lability, visual disturbances, palpitations, diarrhea, irritability.

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

Adverse reactions observed in clinical trials involving children

The following adverse reactions have been observed in clinical trials involving children: Emotional lability (including self-harm, suicidal ideation, suicide attempts, tearfulness, and mood swings), bleeding, hostility, decreased appetite, tremors, increased sweating, hyperkinesia, and agitation. Suicidal ideation and suicide attempts were mostly observed in clinical trials involving adolescents with moderate to severe depressive episodes and recurrent depressive disorder. Hostility has been observed particularly in children with obsessive-compulsive disorder, especially those younger than 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 one-week intervals to a dose of 10 mg per day for one week), symptoms such as emotional lability, nervousness, dizziness, nausea, and abdominal pain were observed in at least 2% of patients when the paroxetine dose was reduced or after complete drug withdrawal and occurred at least 2 times as often as in the placebo group.

Overdose

Symptoms

The available information on paroxetine overdose suggests a wide range of safety.

In paroxetine overdose, fever, changes in blood pressure, involuntary muscle contractions, anxiety, and tachycardia have been observed in addition to the symptoms described in the side effects section.

Patients generally normalized without serious consequences, even with single doses up to 2000 mg. A number of reports have described symptoms such as coma and ECG changes, cases of death have been very rarely observed, usually reported in situations in which patients took paroxetine with or without other psychotropic medications with or without alcohol.

Treatment

The specific antidote for paroxetine is not known. Treatment should include the general measures used for overdose with any antidepressants. Supportive therapy and frequent monitoring of basic physiological parameters, as well as close monitoring are indicated. The patient should be treated according to the clinical picture or according to the recommendations of the national poison center, if available.

Pregnancy use

Fertility

In animal studies, paroxetine may affect semen quality characteristics.

The data from in vitro human studies may indicate some effect on semen quality characteristics, but case reports of human use of some SSRIs (including paroxetine) have shown that the effects on semen quality characteristics were reversible.

To date, no effects on fertility in humans have been observed.

Pregnancy

The teratogenic or selective embryotoxic activity of paroxetine has not been shown in animal studies.

Epidemiological studies of pregnancy outcomes when taking antidepressants in the first trimester indicate an increased risk of congenital abnormalities, particularly cardiovascular (e.g., interventricular and interatrial septal defects), associated with paroxetine intake. The reported incidence of cardiovascular defects in neonates when paroxetine is used during pregnancy is approximately 1/50 compared to the expected incidence of such defects in the general population, which is approximately 1/100 of neonates.

When prescribing paroxetine, the physician should consider alternative treatments for pregnant and planning women. Paroxetine should be prescribed only if its potential benefit exceeds the possible risk. If the decision is made to discontinue paroxetine treatment during pregnancy, the physician should follow the recommendations in the Administration and Dosage (“Discontinuation of Paroxetine”) and the Special Instructions (“Symptoms Observed When Discontinuing Paroxetine Treatment in Adults”) sections.

Preterm births have been reported in women who received paroxetine or other SSRIs during pregnancy, but a causal relationship between these drugs and preterm births has not been established.

The health of newborns whose mothers took paroxetine in late pregnancy should be monitored, because there have been reports of neonatal complications associated with the use of paroxetine or other SSRIs in the third trimester of pregnancy. However, a causal relationship between these complications and this drug therapy has not been confirmed. Described clinical complications included: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, arterial hypertension, arterial hypotension, hyperreflexia, tremor, hypervigilance, irritability, lethargy, persistent crying, and somnolence. Some reports have described the symptoms as neonatal manifestations of withdrawal syndrome. In most cases, the described complications occurred immediately after delivery or shortly thereafter (< 24 h). According to epidemiological studies, taking SSRIs (including paroxetine) during pregnancy, particularly in the late term, is associated with an increased risk of persistent pulmonary hypertension in newborns. The increased risk is observed in children born to mothers who took SSRIs in late pregnancy and is 4-5 times greater than that observed in the general population (1-2 per 1,000 pregnancies).

The results of animal studies suggest reproductive toxicity of the drug, but no direct adverse effects on pregnancy, embryonic and fetal development, labor, or postnatal development were found.

Breastfeeding period

Significant amounts of paroxetine penetrate into breast milk. In published studies in breastfed infants, the serum concentration of paroxetine was undetectable (<2 ng/mL) or very low (<4 ng/mL).

In children, no evidence of drug exposure was detected. However, paroxetine should not be taken during breastfeeding unless its benefit to the mother exceeds the potential risks to the baby.

Similarities