Plisil N, 20 mg 30 pcs.

Indications

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

In the treatment of depressive disorders, paroxetine is about as effective as tricyclic antidepressants. There is evidence that paroxetine may give good results in patients where standard antidepressant therapy has been ineffective.

Paroxetine administration in the morning has no adverse effect on the quality and duration of sleep. In addition, sleep may improve as the effects of paroxetine treatment manifest themselves.

When using short-acting sleeping pills in combination with antidepressants, no additional side effects occurred. In the first few weeks of therapy, paroxetine is effective in reducing symptoms of depression and suicidal ideation.

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

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

Paroxetine has also been effective in preventing relapses of OCD.

. Paroxetine is effective in the treatment of 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 treating panic disorder than the isolated use of cognitive behavioral therapy.

In addition, paroxetine was effective in preventing recurrences of panic disorder.

Paroxetine is an effective treatment for social phobia, including as long-term maintenance and preventive therapy.

. Paroxetine is effective in generalized anxiety disorder, including as maintenance and preventive therapy. Paroxetine is also effective in preventing relapses in this disorder.

Paroxetine is effective in treating post-traumatic stress disorder.

Active ingredient

Composition

How to take, the dosage

Paroxetine is recommended to be taken once a day in the morning with a meal. The tablet should be swallowed whole without chewing.

The recommended dose in adults is 20 mg daily. If necessary, depending on the therapeutic effect, the daily dose may be increased weekly by 10 mg per day up 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 further depending on clinical indications.

In order to relieve depressive symptoms and prevent relapses, it is necessary to observe adequate duration of relieving and maintenance therapy. This period may be several months.

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 may be increased to 60 mg daily. Adequate duration of therapy (several months or longer) should be observed.

The recommended dose is 40 mg daily. Patients should begin treatment with a dose of
10 mg per day and increase the dose weekly by 10 mg per day, guided by clinical effect. If necessary, the dose can be increased to 60 mg daily.

The low starting dose is recommended to minimize the possible exacerbation of panic disorder symptoms that may occur at the beginning of treatment with any antidepressant. Adequate duration of therapy (several months or longer) should be observed.

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

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

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

General Information

Cancellation of paroxetine

As with other psychotropic medications, abrupt withdrawal of paroxetine should be avoided.

The following pattern of withdrawal may be recommended: reducing the daily dose by 10 mg per week; after reaching a dose of 20 mg per day, patients continue taking that dose for one week and only then withdraw the drug completely.

If withdrawal symptoms develop during dose reduction or after withdrawal of the drug, it is reasonable to resume the previously prescribed dose. The doctor may continue reducing the dose at a slower pace thereafter.

Special patient groups

. Elderly patients may have elevated plasma concentrations of paroxetine, 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.

. Plasma paroxetine concentrations 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 prescribed doses of the drug that are in the lower part of the therapeutic dose range.

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-HT receptors (serotonin syndrome). Caution and close clinical monitoring are required when concomitant use of serotonergic drugs (such as L-tryptophan, tryptans, tramadol, SSRIs, lithium, fentanyl and St. John’s wort) with paroxetine.

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

Pimozide

In a study of concomitant use of paroxetine and pimozide at a single low dose (2 mg), increased levels of pimozide were reported. This effect is due to the known property of paroxetine to inhibit the CYP2D6 system. Due to the narrow therapeutic index of pimozide and its known ability to prolong the QT interval, simultaneous use of pimozide and paroxetine is contraindicated.

Enzymes involved in drug metabolism

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

When using paroxetine concomitantly with an enzyme inhibitor involved in drug metabolism, paroxetine should be recommended at a dose that is at the lower end of the therapeutic dose range. The initial dose of paroxetine does not need to be 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 concomitant use of fosamprenavir/ritonavir with paroxetine resulted in a significant decrease in plasma paroxetine concentrations.

The plasma concentrations of fosamprenavir/ritonavir when concomitantly used with paroxetine were similar 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 subsequent dose adjustment of paroxetine should be determined by its clinical effect (tolerability and efficacy).

Procyclidine

Daily administration of paroxetine significantly increases the plasma concentration 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 SSRI group may decrease plasma cholinesterase activity, resulting in increased duration of neuromuscular blocking action of mivacurium and suxamethonium.

Paroxetine’s ability to inhibit the isoenzyme CYP2D

. Like other antidepressants, including other drugs in the SSRI group, paroxetine inhibits the hepatic CYP2D6 isoenzyme of the cytochrome P450 system. Inhibition of CYP2D6 isoenzyme 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 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, consequently, decrease the effectiveness of tamoxifen.

CYP3A4

The in vivo interaction study of paroxetine and terfenadine, which is a substrate of the CYP3A4 isoenzyme, showed that paroxetine did not affect the pharmacokinetics of terfenadine under equilibrium conditions. In a similar in vivo interaction study, paroxetine was found to have no effect on the pharmacodynamics of alprazolam, and vice versa. Concomitant use of paroxetine with terfenadine, alprazolam and other drugs that serve as substrates of CYP3A4 isoenzyme is unlikely to cause harm to the patient.

Drugs that affect gastric pH

Clinical studies have shown that the absorption and pharmacokinetics of paroxetine are independent or almost independent (that is, the existing dependence requires no change in dose) of:

Peroral anticoagulants

Possible pharmacodynamic interaction between paroxetine and oral anticoagulants. Concomitant use of paroxetine and oral anticoagulants may cause increased activity of anticoagulants and risk of bleeding. Therefore, paroxetine should be used with caution to treat patients receiving oral anticoagulants.

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

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, COX-2 inhibitors), and when treating patients with a history of clotting disorders or conditions that may cause a predisposition to bleeding.

Special Instructions

Children and adolescents (under 18 years)

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

Treatment with antidepressants in children and adolescents with major depressive disorder and other mental illnesses is associated with an increased risk of suicidal ideation and suicidal behavior.

In clinical trials, adverse reactions associated with suicide attempts and suicidal ideation and hostility (predominantly aggression, deviant behavior, and anger) were more frequently observed 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 for children and adolescents that address the drug’s effects on growth, maturation, cognitive and behavioral development.

Clinical impairment and suicidal risk in adults

Young patients, especially those with major depressive disorder, may be at increased risk for suicidal behavior during paroxetine therapy. An analysis of cited placebo-controlled studies in adults with mental illness indicates an increased incidence of suicidal behavior in young patients (aged
18-24 years) on paroxetine compared to the placebo group: 17/776 (2.19%) versus 5/542 (0.92%), respectively, although this difference is not considered statistically significant. No increase in the frequency of suicidal behavior was observed in patients in the older age groups (25 to 64 years old and over 65 years old). In adults of all age groups with major depressive disorder, there was a statistically significant increase in suicidal behavior during treatment with paroxetine compared to the placebo group (occurrence 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. The data from the study of patients with major 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 of the disorder and/or the occurrence of suicidal thoughts and suicidal behavior (suicidality) may be observed regardless of whether they receive antidepressants. This risk persists until significant remission is achieved. The patient may not improve in the first weeks of treatment or more, so the patient’s condition should be monitored for timely detection of clinical exacerbation and suicidality, especially at the beginning of treatment, and during periods of dose changes, regardless of dose increases or decreases. Clinical experience with all antidepressants shows that the risk of suicide may increase in the early stages of recovery.

Other psychiatric disorders treated with paroxetine may also be associated with an increased risk of suicidal behavior. In addition, these disorders may represent comorbid conditions accompanying major depressive disorder. Therefore, the same precautions should be taken when treating patients with other psychiatric disorders as when treating major depressive disorder.

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, and therefore all should be given special attention during treatment. Patients (and their caregivers) should be warned to watch for deterioration (including the development of new symptoms) and/or the appearance of suicidal behavior or thoughts of self-harm throughout treatment, especially at the beginning of treatment, or during dose changes (increasing or decreasing). If these symptoms occur, medical attention should be sought immediately.

We should remember that the onset of symptoms such as agitation, akathisia or mania may be related to either the underlying disease 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, especially if they appear suddenly, if their manifestations become increasingly severe, or if they were not part of a previous symptom complex in this patient, the therapy should be reviewed until the drug is discontinued.

Akathisia

In rare cases, treatment with paroxetine or another SSRI medication is accompanied by akathisia, which is manifested by feelings of inner restlessness and psychomotor agitation, where the patient cannot sit or stand quietly; akathisia usually involves subjective discomfort for the patient. Akathisia is most likely to occur in the first few weeks of treatment.

Serotonin syndrome, malignant neuroleptic syndrome

. Serotonin syndrome or symptoms similar to malignant neuroleptic syndrome may occur in rare cases during treatment with paroxetine, especially if paroxetine is used in combination with other serotoninergic drugs and/or neuroleptics. These syndromes may be potentially life-threatening, so treatment with paroxetine should be stopped 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, changes in mental status including confusion, irritability, extreme agitation progressing to delirium and coma) and initiate supportive symptomatic therapy. Paroxetine should not be used in combination with serotonin precursors (such as L-tryptophan, oxytriptan) due to 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 studies) 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 for bipolar disorder; this screening should include a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression.

Paroxetine is not registered 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.

Diabetes

In patients with diabetes, treatment with SSRIs may affect glycemic control. Adjustment of the dose of insulin and/or oral hypoglycemic drugs may be required.

IMAOs

Paroxetine treatment should be started cautiously 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 is achieved.

Renal or hepatic impairment

We recommend caution when treating patients with severe renal impairment or patients with impaired hepatic function with paroxetine.

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

In treatment with paroxetine, hyponatremia occurs rarely and mostly in elderly patients and is reversed after paroxetine withdrawal.

Bleeding

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

Heart disease

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

Symptoms that may occur when discontinuing treatment with paroxetine in adults

According to the results of clinical trials in adults, the incidence of adverse reactions when discontinuing treatment in patients taking paroxetine was 30%, whereas the incidence of adverse reactions in the placebo group was 20%. Withdrawal symptoms do not mean the drug is abused or addictive, as is the case with narcotics and psychotropics.

The following withdrawal symptoms have been described: dizziness, sensory disturbances (including paresthesias, electric shock and tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, tremors, confusion, increased sweating, headache and diarrhea, palpitations, emotional lability, irritability and visual disturbances. These symptoms are usually mild to moderate, but may be severe in some patients. They usually occur in the first few days after withdrawal of the drug, but in very rare cases they occur in patients who have accidentally missed a dose. These symptoms usually go away spontaneously and disappear within
2 weeks, but in some patients they may last 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 discontinuing treatment in patients taking paroxetine was 32%, whereas the incidence of adverse reactions in the placebo group was 24%.

After discontinuation of paroxetine, 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, as well as nervousness, dizziness, nausea and abdominal pain.

Bone fractures

Epidemiological studies of the risk of bone fractures have found an association of bone fractures with taking some antidepressants, including drugs in the SSRI group. The risk was observed during the course of antidepressant treatment and was maximal at the beginning of therapy. The possibility of bone fractures should be considered when using paroxetine.

Tamoxifen

Some studies have shown that the efficacy of tamoxifen, measured in risk of breast cancer recurrence and mortality, may be reduced when combined with paroxetine due to irreversible inhibition of the CYP2D6 isoenzyme. The risk may increase with long-term co-administration. When using tamoxifen to treat or prevent breast cancer, consider using alternative antidepressants that have no or less inhibitory effect on the CYP2D6 isoenzyme.

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRIs)/serotonin and noradrenaline reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see side effects). There have been reports of prolonged sexual dysfunction where symptoms continued despite discontinuation of SSRIs/SRIs.

Influence on ability to operate vehicles and machinery

The 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.

Although paroxetine does not increase the negative effects of alcohol on psychomotor functions, it is not recommended to use paroxetine and alcohol at the same time.

Synopsis

Contraindications

Paroxetine treatment is allowed:

A one-week interval (at least) between discontinuation of paroxetine and initiation of therapy with any DMARD is recommended.

Side effects

The frequency and intensity of some of the paroxetine adverse reactions listed below may decrease as treatment continues, and such reactions do not usually require withdrawal of the drug. The adverse reactions presented below are listed according to organ and organ system involvement and frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), frequent(≥1/100, < 1/10), not common (≥1/1000, < 1/100), rare (≥1/10000, < 1/1000), very rarely (< 1/10000), including individual cases, and frequency unknown.

The incidence of frequent and infrequent adverse reactions was determined based on pooled drug safety data from more than 8,000 patients enrolled 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-registration data, and it refers to the frequency of reported reactions rather than the true incidence of the reactions themselves.

Frequency of adverse reactions

Blood and lymphatic system disorders

Infrequent: Pathological bleeding, mainly bleeding in the skin and mucous membranes (including ecchymosis).

Very rare: thrombocytopenia.

Immune system disorders

Very rare: severe allergic reactions (including anaphylactoid reactions and angioedema).

Endocrine system disorders

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 is sometimes due to inadequate antidiuretic hormone secretion syndrome.

Mental disorders

Often: somnolence, insomnia, agitation, abnormal dreams (including nightmares).

Infrequent: confusion, hallucinations.

Rare: manic reactions, anxiety, depersonalization, panic attacks, akathisia. Frequency unknown: suicidal thoughts and suicidal behavior, teeth grinding.

Incidents of suicidal thoughts and suicidal behavior have been reported during treatment with paroxetine or early after discontinuation of treatment.

These symptoms may also be due to the disease itself.

Nervous system disorders

Often: dizziness, tremor, headache, impaired concentration. Infrequent: extrapyramidal disorders.

Rare: seizures, restless legs syndrome.

Very rare: 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 reported in patients with impaired motor function or who have used neuroleptics.

Visual disturbances

Often: blurred vision.

Infrequent: mydriasis.

Very rare: acute glaucoma.

Hearing and balance disorders

Prevalence unknown: tinnitus.

Cardiac disorders

Infrequent: sinus tachycardia.

Rarely: bradycardia.

Vascular disorders

Infrequent: postural hypotension, transient rise and fall of blood pressure.

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

Respiratory, chest and mediastinal disorders

Often: yawning.

Gastrointestinal tract disorders

Very common: nausea.

Often: constipation, diarrhea, vomiting, dry mouth.

Very rare: gastrointestinal bleeding.

Liver and biliary tract disorders

Rarely: increased liver enzyme activity.

Very rare: adverse reactions on the liver (such as hepatitis, sometimes accompanied by jaundice and/or liver failure).

An increase in 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 rare. The appropriateness of discontinuing treatment with paroxetine should be considered in cases of prolonged elevation of liver function tests.

Skin and subcutaneous tissue disorders

Often: increased sweating.

Infrequent: skin rashes, itching.

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

Recreational and urinary tract disorders

Infrequent: urinary retention, urinary incontinence.

Renital and breast disorders

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

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. Infrequent: agitation, nausea, tremor, confusion, increased sweating, emotional lability, visual disturbances, palpitations, diarrhea, irritability.

The abrupt discontinuation of the drug causes withdrawal syndrome. As with withdrawal from other psychotropic medications, discontinuation of paroxetine (especially abrupt) may cause symptoms such as: dizziness, sensory disturbances (including paresthesias, feeling of electric shocks and tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, headache, tremors, confusion, diarrhea, increased sweating, palpitation, 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 in children

The following adverse reactions have been observed: 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 studies in adolescents with major depressive disorder. Hostility has been observed in children with obsessive-compulsive disorder, particularly in children younger than 12 years of age.

. In clinical studies, a gradual reduction in the daily dose (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) caused paroxetine withdrawal symptoms (emotional lability, nervousness, dizziness, nausea and abdominal pain), which were recorded in at least 2% of patients against a reduced dose of paroxetine or after its complete withdrawal and occurred at least 2 times more often than in the placebo group.

Overdose

Symptoms

The available information on paroxetine overdose indicates a wide range of safety. When 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 usually 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; deaths have been very rare, usually in situations in which patients have taken paroxetine with other psychotropic drugs or with alcohol.

Treatment

The specific antidote for paroxetine is unknown. Treatment should consist of the general measures used in overdose of any antidepressants. Supportive therapy and frequent monitoring of basic physiological parameters are indicated. The patient should be treated according to the clinical picture or in accordance with the recommendations of the national poison center.

Pregnancy use

Fertility

In animal studies, paroxetine may affect semen quality characteristics. Data from human studies in vitro 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 human fertility have been observed.

Pregnancy

Animal studies have shown no teratogenic or selective embryotoxic activity with paroxetine.

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

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

There have been reports of preterm births in women who received paroxetine or other selective serotonin reuptake inhibitors (SSRIs) during pregnancy, although a causal relationship between taking these drugs and preterm births has not been established.

The health of newborns whose mothers took paroxetine late in pregnancy should be monitored, because there have been reports of complications in newborns exposed to paroxetine or other SSRIs in the third trimester of pregnancy. However, a causal relationship between these complications and these drug therapies has not been confirmed.

The clinical complications described included: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, arterial hypertension, arterial hypotension, hyperreflexia, tremor, increased neuroreflexivity syndrome, irritability, lethargy, persistent crying and sleepiness. 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 hours).

According to epidemiological studies, taking SSRIs (including paroxetine) during pregnancy, especially in the late term, is associated with an increased risk of developing persistent pulmonary hypertension in newborns. An increased risk is observed in children born to mothers taking 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 have shown reproductive toxicity of the drug, but no direct adverse effects on pregnancy, embryonic and fetal development, labor, or postnatal development have been shown.

Breastfeeding period

Significant amounts of paroxetine penetrate into breast milk. In published studies in breastfed infants, paroxetine concentrations were undetectable (< 2 ng/mL) or very low
(< 4 ng/mL). No evidence of drug exposure was detected in children. However, paroxetine should not be taken during breastfeeding unless its benefit to the mother exceeds the potential risks to the baby.

Similarities