Instructions Paroxin film-coated tablets 20 mg blister No. 60
Composition
active ingredient: paroxetine hydrochloride hemihydrate;
1 tablet contains paroxetine hydrochloride hemihydrate equivalent to paroxetine 20 mg;
excipients: calcium hydrogen phosphate dihydrate, sodium starch glycolate (type A), microcrystalline cellulose, magnesium stearate, coating for applying the shell Opadry II White (polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide (E 171)).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets, with a biconvex surface, with a score, covered with a white film coating.
Pharmacotherapeutic group
Antidepressants. ATX code N06A B05.
Pharmacological properties
Pharmacodynamics
Paroxetine is a potent selective 5-hydroxytryptamine (5-HT, serotonin) reuptake inhibitor. Its antidepressant action and efficacy in the treatment of obsessive-compulsive and panic disorders are due to the specific inhibition of 5-hydroxytryptamine uptake by brain neurons. Paroxetine differs in its chemical structure from tricyclic, tetracyclic and other known antidepressants.
The drug has low affinity for muscarinic cholinergic receptors. Unlike tricyclic antidepressants, it has low affinity for alpha1-, alpha2- and beta-adrenergic receptors, dopamine (D2), 5-HT1-like, 5-HT2- and histamine (H1-) receptors; it does not affect psychomotor function and does not enhance the depressive effect of ethanol.
The drug Paroxin does not affect the activity of the cardiovascular system, does not cause clinically significant changes in blood pressure, heart rate, and ECG parameters.
The drug Paroxin, unlike antidepressants that inhibit norepinephrine uptake, has a much smaller effect on the hypotensive effect of guanethidine.
Pharmacokinetics
After oral administration, it is rapidly absorbed and undergoes transformation in the liver.
The main metabolites of paroxetine are polar and conjugated oxidation and methylation products, which are rapidly excreted from the body.
Approximately 64% of an administered dose of paroxetine is excreted in the urine, with less than 2% excreted as unchanged paroxetine. Approximately 36% of an administered dose of paroxetine is excreted in the feces as metabolites.
Paroxetine metabolites are eliminated in 2 stages - first by first-pass metabolism through the liver, and then by systemic elimination of paroxetine.
The half-life is on average approximately 1 day.
A constant concentration in the blood is achieved 7-14 days after the start of treatment, and during subsequent long-term treatment, the pharmacokinetics of the drug almost does not change.
No correlation was found between paroxetine plasma concentrations and clinical effect (efficacy and adverse reactions).
Due to the breakdown of the drug in the liver, the amount of paroxetine circulating in the blood is less than the amount absorbed from the gastrointestinal tract. With an increase in a single dose or with repeated dosing, the effect of partial saturation of the metabolic pathway of the first pass through the liver occurs and a decrease in plasma clearance is observed. This leads to a disproportionate increase in the concentration of paroxetine in the blood plasma and changes in pharmacokinetic parameters with the appearance of a nonlinear relationship. However, such nonlinearity is mostly insignificant and is observed only in patients in whom low doses achieve a low concentration of the drug in the blood plasma.
Paroxetine is widely distributed in body tissues. Calculated pharmacokinetic parameters indicate that only 1% of the administered dose remains in the blood plasma.
When used in therapeutic concentrations, approximately 95% of paroxetine is bound to plasma proteins.
In elderly patients and patients with renal or hepatic insufficiency, an increase in the concentration of paroxetine in the blood plasma is observed, but it does not exceed the concentration fluctuations in healthy adult volunteers.
Indication
Adults
Major depressive disorder. Treatment of major depressive disorder.
Obsessive-compulsive disorder. Treatment of symptoms and prevention of relapse of obsessive-compulsive disorder.
Panic disorder. Treatment of symptoms and prevention of relapses of panic disorder with or without concomitant agoraphobia.
Social phobias/social anxiety disorders. Treatment of social phobias/social anxiety disorders.
Generalized anxiety disorder. Treatment of symptoms and prevention of relapse of generalized anxiety disorder.
Post-traumatic stress disorder. Treatment of post-traumatic stress disorder.
Contraindication
Hypersensitivity to paroxetine or to any of the other ingredients of the drug.
Similarly, MAO inhibitors should not be used until 2 weeks after stopping paroxetine treatment (see section “Interaction with other medicinal products and other types of interactions”).
The drug should not be used in combination with thioridazine, since, like other drugs that inhibit the hepatic enzyme CYP450 2D6, paroxetine may increase thioridazine levels (see section "Interaction with other medicinal products and other forms of interaction"). The use of thioridazine may cause prolongation of the QT interval with associated severe ventricular arrhythmia (e.g. torsades de pointes) and sudden death. The drug Paroxin should not be prescribed in combination with pimozide (see section "Interaction with other medicinal products and other forms of interaction").
Interaction with other medicinal products and other types of interactions
Serotonergic drugs
As with other selective serotonin reuptake inhibitors (SSRIs), concomitant use with serotonergic drugs may lead to a 5-HT-associated effect (serotonin syndrome).
Paroxetine should be used with caution and with careful clinical monitoring of the patient with serotonergic drugs such as L-tryptophan, triptans, tramadol, other serotonin reuptake inhibitors, lithium, fentanyl, buprenorphine and St. John's wort. Concomitant use of paroxetine with MAO inhibitors, including linezolid, an antibiotic that is also a reversible non-selective MAO inhibitor, and methylthioninium chloride (methylene blue), is contraindicated (see section 4.3).
Pimozide
A study of the co-administration of a single low dose of pimozide (2 mg) and paroxetine showed an increase in pimozide levels. This was explained by the known CYPD26 inhibitory properties of paroxetine. Due to the narrow therapeutic index of pimozide and its potential to prolong the QT interval, the concomitant use of pimozide and paroxetine is contraindicated (see section 4.3).
Enzymes involved in drug metabolism
The metabolism and pharmacokinetic parameters of paroxetine may be altered by induction or inhibition of enzymes involved in drug metabolism.
When paroxetine is used concomitantly with enzyme-inhibiting drugs, it is recommended to use the lowest effective dose. When used concomitantly with enzyme-inducing drugs (carbamazepine, rifampicin, phenobarbital, phenytoin), there is no need to change the initial dose of paroxetine. The dose should be adjusted during further treatment according to the clinical effect (tolerability and efficacy).
Muscle relaxants
SSRIs may reduce plasma cholinesterase activity, leading to a prolongation of the neuromuscular blocking effect of mivacurium and suxamethonium.
Fosamprenavir/ritonavir
Co-administration of fosamprenavir/ritonavir with paroxetine significantly reduces plasma levels of paroxetine. Dosage adjustments during subsequent treatment should be based on clinical response (tolerability and efficacy).
Procyclidine
Daily use of paroxetine significantly increases serum procyclidine levels. If anticholinergic effects occur, the procyclidine dose should be reduced.
Anticonvulsants
Carbamazepine, phenytoin, sodium valproate. When used simultaneously with these drugs, no effect on the pharmacokinetics/pharmacodynamics of the drug is observed in patients with epilepsy.
The ability of paroxetine to inhibit the CYP2D6 enzyme
Paroxetine, like other antidepressants that are serotonin reuptake inhibitors, inhibits the activity of the cytochrome P450 enzyme CYP2D6. Inhibition of CYP2D6 may lead to increased plasma concentrations of concomitantly administered drugs that are metabolized by this enzyme. These drugs include some tricyclic antidepressants (e.g., amitriptyline, nortriptyline, imipramine, and desipramine), phenothiazine neuroleptics (e.g., perphenazine and thioridazine), risperidone, atomoxetine, some type 1c antiarrhythmics (e.g., propafenone and flecainide), and metoprolol.
Tamoxifen has an important active metabolite, endoxifen, which is produced by CYP2D6 and is an important component of tamoxifen's efficacy. Irreversible inhibition of CYP2D6 by paroxetine results in decreased plasma concentrations of endoxifen (see section 4.4).
CYP3A4
In in vivo experiments, the concomitant use of paroxetine and terfenadine, a substrate for the CYP3A4 enzyme, when achieving a constant blood concentration was not accompanied by an effect of paroxetine on the pharmacokinetics of terfenadine. A similar in vivo interaction study did not reveal any effect of the drug on the pharmacokinetics of alprazolam and vice versa. The simultaneous administration of paroxetine and terfenadine, alprazolam and other drugs that are substrates for CYP3A4 may not be dangerous.
The drug Paroxetine does not increase the impairment of mental and motor reactions caused by alcohol, however, drinking alcoholic beverages during treatment with paroxetine is not recommended.
Oral anticoagulants
Concomitant use of oral anticoagulants and paroxetine may result in a pharmacodynamic interaction that may lead to increased anticoagulant activity and bleeding risk. Therefore, paroxetine should be administered with caution to patients treated with oral anticoagulants.
Nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and antiplatelet agents
When NSAIDs/acetylsalicylic acid are used concomitantly with paroxetine, a pharmacodynamic interaction may occur, which may lead to an increased risk of bleeding. Paroxetine should be administered with caution in conjunction with drugs that affect platelet function or increase the risk of bleeding.
Pravastatin
The interaction between paroxetine and pravastatin observed in studies suggests that concomitant use of paroxetine and pravastatin may lead to an increase in blood glucose levels. Diabetic patients receiving both paroxetine and pravastatin may require dosage adjustments of oral hypoglycemic agents and/or insulin (see section 4.4).
Application features
Children and adolescents
Treatment with antidepressants is associated with an increased risk of suicidal behaviour and thoughts in children and adolescents with major depressive disorder and other psychiatric disorders. It is known that, according to clinical trials, side effects related to suicidality (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and irritability) were observed more often in children and adolescents treated with paroxetine compared to placebo (see section "Adverse reactions"). The results of the study of the safety of the drug in children and adolescents with regard to growth, development, cognitive and behavioural characteristics are not available.
Clinical deterioration and suicide risk in adults
Younger adults, particularly those with major depressive disorder, may be at increased risk of suicidal behaviour when treated with paroxetine. It is known that in an analysis of placebo-controlled clinical trials in adults with psychiatric disorders, young adults (approximately 18-24 years of age) were at greater risk of suicidal behaviour than placebo-treated patients (17 of 776 (2.19%) compared with 5 of 542 (0.92%)), although this difference was not statistically significant. This increased risk was not observed in older patients (25-64 years of age and 65 years of age and older). In patients with major depressive disorder (of any age) treated with paroxetine, there was a statistically significant increase in the incidence of suicidal behaviour compared with placebo (11 of 3455 (0.32%) compared with 1 of 1978 (0.05%), all of which were suicide attempts). However, the majority of such attempts (8 of 11) during paroxetine treatment occurred in young adults aged 18–30 years. These data on the treatment of major depressive disorder suggest that the higher risk of these complications observed in the group of young patients with psychiatric disorders may extend to patients aged 24 years and older.
Patients with depressive disorders may experience worsening of depressive symptoms and/or suicidal ideation and behavior (suicidality) whether or not they are taking antidepressants. This risk persists until significant remission occurs. It is a general clinical experience with all courses of antidepressants that the risk of suicide may increase in the early stages of recovery.
Other psychiatric disorders for which paroxetine is prescribed may be associated with an increased risk of suicidal behaviour, and such disorders may also be co-occurring with major depressive disorder. In addition, patients with a history of suicidal behaviour and thoughts, young patients, and patients with a persistent suicidal ideation prior to commencement of treatment are at increased risk of suicide attempts and suicidal thoughts. All patients should be observed closely for clinical worsening (including the development of new symptoms) and suicidal behaviour during treatment, particularly at the beginning of treatment or at the time of dose changes (both increases and decreases). Patients (and caregivers of patients) should be warned about the need to constantly monitor for any worsening of the patient's condition (including the development of new symptoms) and/or the emergence of suicidal thoughts/behavior or thoughts of harming themselves and about the need to seek medical advice immediately if they appear.
A change in therapeutic regimen, including discontinuation of the drug, should be considered for patients with clinical worsening (including development of new symptoms) and/or emergence of suicidal ideation/behavior, especially if these symptoms are severe, sudden in onset, or not part of the patient's previous symptom complex.
Akathisia
Rarely, the use of paroxetine or other SSRIs may be associated with the development of akathisia, a condition characterised by a feeling of inner restlessness and psychomotor agitation, such as an inability to sit or stand still, combined with a subjective feeling of discomfort. This is most likely to occur during the first weeks of treatment.
Serotonin syndrome/neuroleptic malignant syndrome
In isolated cases, treatment with paroxetine may be associated with the development of serotonin syndrome or symptoms characteristic of neuroleptic malignant syndrome, especially when used concomitantly with other serotonergic and/or neuroleptic drugs. Since these syndromes can cause life-threatening conditions, treatment with paroxetine should be discontinued in the event of such phenomena (characterized by a combination of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid changes in the main indicators of the functional state of the body, changes in mental status, including confusion, irritability, borderline agitation with progression to delirium and coma) and supportive symptomatic therapy should be prescribed. Paroxetine should not be used in combination with serotonin precursors (such as L-tryptophan, oxitriptan) due to the risk of serotonin syndrome (see sections "Contraindications" and "Interaction with other medicinal products and other types of interactions").
Mania and bipolar disorders
A major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although not supported by data from controlled clinical trials) that treatment of such episodes with an antidepressant alone may increase the likelihood of accelerated onset of mixed/manic episodes in patients at increased risk of developing bipolar disorder. Before starting treatment with antidepressants, patients should be carefully evaluated to identify any risk factors for bipolar disorder. Such evaluation should include a detailed history of the patient, including the presence of suicide attempts, bipolar disorder and depression in family members. It should be noted that paroxetine is not used to treat depression in bipolar disorder. As with other antidepressants, paroxetine should be used with caution in patients with a history of manic episodes.
Tamoxifen
Studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer recurrence/fatality, may be reduced when co-administered with paroxetine, as paroxetine is an irreversible inhibitor of CYP2D6 (see section 4.5). This risk increases with the duration of co-administration. When treating breast cancer with tamoxifen, the patient should be given an alternative antidepressant with little or no CYP2D6 inhibition.
Bone fractures
Epidemiological studies investigating the risk of bone fractures with the use of some antidepressants, including SSRIs, have reported an association with fractures. The risk appears to be treatment-emergent and is highest in the early stages of therapy. The possibility of bone fractures should be considered when treating with paroxetine.
Monoamine oxidase inhibitors
Treatment with paroxetine should be initiated with caution, not earlier than 2 weeks after discontinuation of MAO inhibitors; the dose should be increased gradually until an optimal response is achieved.
Renal/hepatic failure
It is recommended to use with caution in the treatment of patients with severe renal or hepatic insufficiency.
Diabetes mellitus
In patients with diabetes mellitus, treatment with serotonin reuptake inhibitors may alter the glycemic profile, therefore the dose of insulin and/or oral hypoglycemic agents should be adjusted. In addition, clinical studies indicate that an increase in blood glucose levels may occur with concomitant treatment with paroxetine and pravastatin.
Epilepsy
Paroxetine, like other antidepressants, should be used with caution in the treatment of patients with epilepsy.
Attacks
The overall incidence of seizures in patients treated with paroxetine is less than 0.1%. If a patient develops seizures, Paroxetine should be discontinued.
Electroconvulsive therapy
There is only limited clinical experience with the use of paroxetine in combination with electroconvulsive therapy.
Glaucoma
The drug Paroxin, like other serotonin reuptake inhibitors, can cause mydriasis, so it should be used with caution in the treatment of patients with angle-closure glaucoma.
Hyponatremia has been reported occasionally, mainly in elderly patients. Symptoms of hyponatremia resolve in most cases after discontinuation of paroxetine.
Hemorrhages
Skin and mucous membrane bleeding (including gastrointestinal and gynaecological bleeding) has been reported following treatment with paroxetine. Therefore, paroxetine should be used with caution in patients receiving concomitant medications that increase the risk of bleeding, or in patients with a history of or predisposition to frequent bleeding. Elderly patients may be at increased risk of non-menstrual bleeding.
SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections “Use during pregnancy or lactation”, “Adverse reactions”).
Heart disease
When treating patients with concomitant cardiac disease, the usual precautions should be observed.
Symptoms observed during paroxetine withdrawal
It is known that in clinical trials in adults, adverse reactions on discontinuation of paroxetine treatment occurred in 30% of patients compared with 20% of patients taking placebo. The occurrence of withdrawal symptoms is not analogous to the situation where addiction or dependence occurs when the drug is abused.
Symptoms such as dizziness, sensory disturbances (including paraesthesia, electric shock sensations and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion, increased sweating, headache, diarrhoea have been reported. These symptoms are generally mild to moderate in nature, although in some patients they may be more severe. They usually occur within the first few days after discontinuation of the drug, but there have been isolated cases of these symptoms in patients who have accidentally missed a dose. These symptoms usually resolve spontaneously within 2 weeks, although in some patients this process may be longer (2-3 months or longer). Therefore, it is recommended that when discontinuing paroxetine, the dose be reduced gradually, over a period of several weeks or months, depending on the individual characteristics of the patient (see section "Method of administration and dosage").
Symptoms observed in children and adolescents during paroxetine withdrawal.
It is known that in clinical trials in children and adolescents, adverse reactions on discontinuation of paroxetine occurred in 32% of patients compared with 24% of patients receiving placebo. The following adverse reactions occurred after discontinuation of paroxetine (with a frequency of at least 2% of patients and with a frequency of occurrence twice that of placebo): emotional lability (including suicidal ideation, suicide attempts, mood swings and tearfulness), nervousness, dizziness, nausea and abdominal pain (see section "Adverse reactions").
Sexual dysfunction
SSRIs may cause symptoms of sexual dysfunction (see section 4.8). In some cases, these symptoms have persisted after discontinuation of SSRI treatment.
Warnings regarding excipients.
Sodium compounds
1 tablet of the medicinal product contains less than 1 mmol (23 mg) of sodium, i.e. this medicinal product can be considered to be essentially sodium-free.
Use during pregnancy or breastfeeding
Fertility
It is known that SSRIs, including paroxetine, have been shown in clinical trials to have an effect on sperm quality. These effects are thought to reverse after treatment is discontinued. Alterations in sperm quality may affect the fertility of some men.
Pregnancy
No teratogenic or embryotoxic effects of paroxetine have been detected in animal studies.
Pregnancy outcome studies in women treated with antidepressants during the first trimester of pregnancy have reported an increased risk of congenital malformations, mainly cardiovascular (e.g. atrial or ventricular septal defect), associated with paroxetine. Based on these data, it can be assumed that the risk of having an infant with a cardiovascular defect in women treated with paroxetine during pregnancy is approximately 1 in 50 compared with the expected risk of such a defect in the general population of approximately 1 in 100.
The physician should consider alternative treatment options for pregnant women or women planning to become pregnant and should only prescribe paroxetine if the expected benefit to the mother outweighs the potential risk to the fetus. If a decision is made to discontinue treatment during pregnancy, the appropriate sections of the prescribing information for the drug should be consulted for further information on dosage and symptoms of discontinuation of paroxetine (see sections 4.2 and 4.4).
Newborns should be examined if paroxetine is continued in the third trimester of pregnancy, as there have been reports of neonatal complications following maternal treatment with paroxetine or other SSRIs during this period, although a causal relationship to the drug has not been established. The following effects have been reported: respiratory distress, cyanosis, apnoea, convulsions, temperature fluctuations, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, irritability, lethargy, persistent crying and somnolence. Some reports have described the symptoms as neonatal withdrawal symptoms. In most cases, they occur immediately or shortly (< 24 hours) after delivery.
Studies have shown that the use of SSRIs (including paroxetine) during pregnancy, especially in late pregnancy, is associated with an increased risk of persistent pulmonary hypertension in the newborn. In women who used SSRIs in late pregnancy, the risk was 4-5 times higher than in the general population (1-2 cases per 1000 pregnancies in the general population).
Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage after exposure to SSRIs/NSAIDs during the month before delivery (see sections “Special warnings and precautions for use” and “Adverse reactions”).
Breastfeeding period
Small amounts of paroxetine are excreted in breast milk. No evidence of effects on the newborn has been found, however, paroxetine should not be used during breast-feeding unless the expected benefit to the mother outweighs the potential risk to the child.
Ability to influence reaction speed when driving vehicles or other mechanisms
Clinical experience with paroxetine suggests that it does not affect cognitive function or psychomotor reactions. However, as with other psychoactive drugs, patients should be warned about the possible impairment of their ability to drive or operate machinery during treatment.
Paroxetine does not enhance the impairment of mental and motor reactions caused by alcohol, however, the combined use of paroxetine and alcohol is not recommended.
Method of administration and doses
General recommendations.
The drug Paroxin should be taken orally, it is recommended to take it once a day, in the morning, during a meal. The tablet should be swallowed without chewing.
As with all other antidepressants, the dose should be carefully titrated individually during the first 2-3 weeks of treatment and then adjusted according to clinical response.
The course of treatment should be long enough to ensure the elimination of symptoms. This period may last several months in the treatment of depression, and even longer in the treatment of obsessive-compulsive and panic disorders. As with other drugs for the treatment of mental disorders, abrupt withdrawal of the drug should be avoided.
Major depressive disorder. The recommended dose is 20 mg per day. Some patients may require an increase in dose. This should be done gradually, increasing the dose by 10* mg (up to a maximum of 50* mg per day) depending on the clinical response to treatment.
Obsessive-compulsive disorder. The recommended dose is 40 mg per day. Treatment should be initiated with a dose of 20 mg and gradually increased by 10* mg weekly. If necessary, the dose may be increased to a maximum dose of 60 mg.
Panic disorder. The recommended dose is 40 mg per day. Treatment should be initiated at 10* mg per day and increased by 10* mg weekly, depending on clinical response. Some patients may only respond to a maximum dose of 60 mg per day.
To reduce the risk of possible worsening of panic disorder symptoms, which is often observed at the beginning of treatment for this disease, it is recommended to start treatment with a low dose of the drug.
Social anxiety disorder/social phobia. The recommended dose is 20 mg per day. For some patients, the dose may be increased gradually by 10* mg per day, depending on the clinical effect of treatment, up to 50* mg per day. The interval between dose increases should be at least 1 week.
Generalized anxiety disorder. The recommended dose is 20 mg per day. For some patients with insufficient efficacy at 20 mg, the dose may be gradually increased by 10* mg per day, depending on the clinical effect, up to 50* mg per day.
Post-traumatic stress disorder. The recommended dose is 20 mg per day. For some patients with insufficient efficacy at 20 mg, the dose may be gradually increased by 10* mg per day, depending on the clinical effect, up to 50* mg per day.
As with other drugs for the treatment of mental illness, abrupt withdrawal of the drug should be avoided. A gradual tapering regimen may be used, involving a reduction in the daily dose by 10* mg per day at weekly intervals. After reaching a dosage regimen of 20 mg per day, patients should continue taking the drug at this dose for another week before completely discontinuing it. If very severe symptoms occur during dose reduction or after discontinuation of treatment, it is necessary to consider reintroducing treatment at the previous dose. Later, the dose can be continued to be reduced, but at a slower rate.
Elderly patients: Treatment should be initiated at the usual adult starting dose, which may then be titrated to 40 mg daily. Elevated plasma concentrations of paroxetine have been reported in elderly patients, but the range of concentrations in this group of patients is similar to that in younger patients.
Children. The drug Paroxin is not indicated for the treatment of children.
Renal and hepatic impairment: In patients with severe renal impairment (creatinine clearance less than 30 ml/min) or hepatic impairment, increased plasma concentrations of paroxetine have been observed. Therefore, the dose should be reduced to the lower end of the dosing range in such patients.
* use paroxetine preparations in the appropriate dosage.
Children.
Paroxetine is not indicated for the treatment of children. It is known that controlled clinical trials have not demonstrated efficacy and no supporting data have been obtained regarding the use of paroxetine for the treatment of children with depression.
Overdose
In case of overdose with paroxetine, in addition to the symptoms mentioned in the "Adverse Reactions" section, increased body temperature, changes in blood pressure, involuntary muscle contractions, anxiety and tachycardia were observed.
All these effects in patients in most cases pass without serious consequences even after taking a dose of 2000 mg. Sometimes coma or changes in ECG parameters were observed, very rarely fatal outcomes were noted, but mainly in such cases paroxetine was used together with other psychotropic drugs or with alcohol.
Specific antidote is unknown.
Treatment of overdose should include general therapeutic measures, the same as for overdose with other antidepressants. Supportive therapy with monitoring of vital signs and careful observation of the patient in a hospital setting is indicated.
Adverse reactions
The side effects listed below are classified by system organ class and frequency. The frequency is defined as: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available data).
Blood and lymphatic system disorders: uncommon - increased bleeding, mainly of the skin and mucous membranes (including ecchymoses and gynecological bleeding); very rare - thrombocytopenia.
Immune system disorders: Very rare: Severe and potentially fatal allergic reactions (including anaphylactoid reactions and angioedema).
On the part of the endocrine system: very rarely, common - syndrome due to insufficient secretion of antidiuretic hormone.
Metabolism and nutrition: common - increased cholesterol levels, decreased appetite; uncommon - there are reports of a changed glycemic profile in patients with diabetes (see section "Special instructions for use"); rare - hyponatremia. Hyponatremia is mainly observed in elderly patients and is sometimes associated with a syndrome caused by insufficient secretion of antidiuretic hormone.
Psychiatric disorders: common - drowsiness, insomnia, agitation, abnormal dreams (including nightmares); uncommon - confusion, hallucinations; rare - manic reactions, restlessness, depersonalization, panic attacks, akathisia; frequency unknown - suicidal ideation, suicidal behavior and aggression. These symptoms may also be due to the underlying disease.
Nervous system disorders: common - dizziness, tremor, headache; uncommon - extrapyramidal disorders; rare - convulsions, akathisia, syringomyelia
