Instructions Paroxetine tablets 20 mg blister No. 30
Composition
active ingredient: paroxetine;
1 tablet contains paroxetine hydrochloride 22.22 mg equivalent to paroxetine 20 mg;
excipients: microcrystalline cellulose, calcium hydrogen phosphate dihydrate, croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: flat tablets of almost white color, with beveled edges, a dividing line on one side and marking "20" on the other. Diameter 9.0 -9.2 mm, height 3.1 - 3.4 mm.
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. Paroxetine, unlike tricyclic antidepressants, has low affinity for alpha1, alpha2- and beta-adrenergic receptors, dopamine (D2), 5-HT1-like, 5-HT2- and histamine (H1-) receptors; does not affect psychomotor function and does not enhance the depressive effect of ethanol.
Paroxetine does not affect the activity of the cardiovascular system; it does not cause clinically significant changes in blood pressure, heart rate and ECG parameters.
Paroxetine, unlike antidepressants that inhibit norepinephrine uptake, has a much smaller effect on the hypotensive effect of guanethidine.
Pharmacokinetics
Paroxetine is rapidly absorbed after oral administration 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% of the dose excreted unchanged. Approximately 36% of the administered dose of paroxetine is excreted in the feces as metabolites.
Paroxetine metabolites are eliminated in two 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 blood concentration 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 administration, the effect of partial saturation of the metabolic pathway of the first passage 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 binds 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 adults.
Indication
Treatment of major depressive disorder. Treatment of symptoms and prevention of relapse of obsessive-compulsive disorder. Treatment of symptoms and prevention of relapse of panic disorder with or without concomitant agoraphobia. Treatment of social phobias/social anxiety disorders. Treatment of symptoms and prevention of relapse of generalized anxiety disorder. Treatment of post-traumatic stress disorder.
Contraindication
Hypersensitivity to paroxetine or any other component of the drug.
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.
Paroxetine should not be administered in combination with pimozide (see section “Interaction with other medicinal products and other types of interactions”).
Interaction with other medicinal products and other types of interactions
Serotonergic drugs
As with other selective serotonin reuptake inhibitors, concomitant use with serotonergic drugs may lead to a 5-HT-associated effect (serotonin syndrome).
Paroxetine should be used with caution with serotonergic drugs such as L-tryptophan, triptans, tramadol, other serotonin reuptake inhibitors, lithium, fentanyl and St. John's wort Hypericum perforatum, and with careful clinical monitoring of the patient. Concomitant use of paroxetine with MAO inhibitors (including linezolid, an antibiotic that is a reversible non-selective MAO inhibitor, and methylthioninium chloride (methylene blue)) is contraindicated (see section "Contraindications").
Pimozide
In a study of the co-administration of a single low dose of pimozide (2 mg) and paroxetine, an increase in pimozide levels was observed. This was explained by the known inhibitory properties of paroxetine on CYPD26. 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
Selective serotonin reuptake inhibitors 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 together 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
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.
In clinical studies, the absorption or pharmacokinetics of paroxetine were found to be unaffected or substantially unaffected (i.e., do not require dosage adjustment) by the following factors: food, antacids, digoxin, propranolol, alcohol.
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.
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 prescribed with caution to patients taking oral anticoagulants.
Nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and antiplatelet agents.
When NSAIDs/acetylsalicylic acid and paroxetine are used together, a pharmacodynamic interaction may occur, which may lead to an increased risk of bleeding.
Caution is recommended when using selective serotonin reuptake inhibitors and oral anticoagulants, drugs that affect platelet function or increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors), as well as when using in patients with a history of bleeding or blood clotting disorders that may cause 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
Antidepressant treatment is associated with an increased risk of suicidal behaviour and thoughts in children and adolescents with major depressive disorder and other psychiatric disorders. In clinical trials, adverse events related to suicidality (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and irritability) were observed more frequently in children and adolescents treated with Paroxetine compared to placebo. There are no data on the safety of the drug on growth, development, cognitive and behavioural characteristics in children and adolescents.
Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide. The risk persists until significant remission occurs. As improvement may not occur within the first weeks of treatment or even longer, close monitoring is necessary until improvement occurs. Based on available clinical experience, the risk of suicide may be increased in the initial phase of recovery.
Other psychiatric conditions for which paroxetine is prescribed may also be associated with an increased risk of suicidal behaviour. In addition, these conditions may accompany major depressive disorder. Therefore, the same precautions should be observed in the treatment of these conditions as in the treatment of major depressive disorder.
It is known that the risk of suicidal thoughts or suicide attempts is increased in patients with a history of such manifestations or suicidal ideation before starting treatment, so they should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants compared with placebo in patients under 25 years of age (see also section "Pharmacodynamics").
Patients should be closely monitored at the start of treatment and when the dose is changed, especially in patients at increased risk. Patients (and caregivers of patients) should be warned about the need to monitor the dynamics of symptoms in order to promptly identify clinical worsening, suicidal behavior or suicidal thoughts, unusual changes in behavior and to seek medical advice immediately if such symptoms appear.
Akathisia
Rarely, the use of paroxetine or other selective serotonin reuptake inhibitors may be associated with the development of akathisia, a condition characterized 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. The likelihood of this condition occurring is highest during the first weeks of treatment.
In isolated cases, treatment with Paroxetine may be associated with the development of serotonin or 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 believed (although not confirmed by controlled clinical trials) that treatment of such episodes with an antidepressant alone increases 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 approved for the treatment of depression in bipolar disorder. As with other antidepressants, Paroxetine should be used with caution in patients with a history of mania.
Sexual dysfunction
Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). Long-term sexual dysfunction has been reported where symptoms persist despite discontinuation of SSRIs/SNRIs.
Tamoxifen
Some 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.
Drugs affecting the pH of gastric juice
In patients taking oral suspensions, the pH of the gastric juice may affect the plasma concentration of paroxetine. In vitro data show that an acidic environment is necessary for the release of the active substance from the suspension, therefore absorption may be reduced in patients with high gastric pH or achlorhydria, as well as after the use of certain drugs (antacids, histamine H2-receptor antagonists, proton pump inhibitors), in concomitant diseases (e.g. atrophic gastritis, pernicious anemia, chronic Helicobacter pylori infection), after surgical interventions (vagotomy, gastrectomy). The pH dependence should be taken into account when changing the dosage form of paroxetine (e.g., plasma concentrations of paroxetine may decrease after switching from tablets to oral suspension in patients with high gastric pH). Therefore, caution is recommended at the beginning and end of treatment with drugs that increase the pH of gastric juice, and a change in dosage may also be required.
Bone fractures
Epidemiological studies investigating the risk of bone fractures with certain antidepressants, including selective serotonin reuptake inhibitors, suggest that the risk arises during treatment and is greatest in the initial stages of therapy. The possibility of bone fractures should be considered when treating patients 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, so 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.
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
Paroxetine, like other serotonin reuptake inhibitors, may cause mydriasis and should be used with caution in patients with angle-closure glaucoma.
Hyponatremia
Hyponatremia has occasionally been reported, predominantly in the elderly. Caution should also be exercised in patients at risk of hyponatremia, such as those with concomitant medication and cirrhosis. Symptoms of hyponatremia generally resolved after discontinuation of paroxetine.
Hemorrhages
Skin and mucous membrane bleeding, such as ecchymoses and purpura, has been reported with SSRIs (including gastrointestinal and gynaecological bleeding). Elderly patients may be at increased risk of non-menstrual bleeding. Therefore, Paroxetine should be used with caution in patients receiving concomitant oral anticoagulants, medicinal products that affect platelet function or other medicinal products that may increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, COX-2 inhibitors), and in patients with a history of or predisposition to bleeding.
SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections “Use during pregnancy or lactation”, “Adverse reactions”).
Heart disease
The usual precautions should be taken when treating patients with concomitant cardiac disease.
Symptoms observed in adults during Paroxetine withdrawal
In clinical trials in adults, adverse reactions on discontinuation of paroxetine occurred in 30% of patients compared with 20% of patients receiving placebo. The symptoms of withdrawal are different from those that occur with drug abuse or dependence. The risk of withdrawal symptoms may depend on several factors, including duration of treatment, dosage, and rate of dose reduction.
Symptoms such as confusion, palpitations, emotional lability, irritability, visual disturbances, dizziness, sensory disturbances (including paraesthesia, electric shock sensations and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, convulsions, 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 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 withdrawal of Paroxetine
In clinical trials in children and adolescents, adverse reactions on discontinuation of paroxetine occurred in 32% of patients compared with 24% of patients on placebo. The following adverse reactions occurred after discontinuation of paroxetine (at least 2% of patients, which was twice as high as in the placebo group): emotional lability (including suicidal ideation, suicide attempts, mood swings and tearfulness), nervousness, dizziness, nausea and abdominal pain (see section 4.8).
Ability to influence reaction speed when driving vehicles or other mechanisms
Experience with Paroxetine in clinical practice indicates that this drug does not affect cognitive function or psychomotor reactions. However, as with other psychoactive drugs, patients should be warned about the possible impairment of the ability to drive or operate machinery during treatment. Paroxetine does not enhance the impairment of mental and motor reactions caused by alcohol, but the combined use of paroxetine and alcohol is not recommended.
Use during pregnancy or breastfeeding
Fertility
Some clinical studies have suggested that selective serotonin reuptake inhibitors, including paroxetine, may have an effect on sperm quality. These effects are thought to reverse after discontinuation of treatment. Changes in sperm quality may affect the fertility of some men.
Pregnancy
Recent epidemiological studies of pregnancy outcomes 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. According to these studies, the risk of having an infant with a cardiovascular defect in a woman 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 package leaflet should be consulted for further information on the dosage and symptoms of discontinuation of paroxetine (see sections 4.2 and 4.4).
There have been reports of premature birth in women treated with paroxetine or other selective serotonin reuptake inhibitors, although a causal relationship to the drug has not been established.
Newborns should be monitored 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, shaking, irritability, lethargy, persistent crying and somnolence. In some reports, symptoms have been described as neonatal withdrawal symptoms. In most cases, they occur immediately or shortly (< 24 hours) after delivery.
Epidemiological studies have shown that the use of selective serotonin reuptake inhibitors (including paroxetine) during pregnancy, particularly in late pregnancy, is associated with an increased risk of persistent pulmonary hypertension of the newborn. In women who used SSRIs in late pregnancy, the risk was 4- to 5-fold 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”).
Breast-feeding
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 breastfeeding unless the expected benefit to the mother outweighs the potential risk to the child.
Method of administration and doses
The drug is intended for oral use, it is recommended to take it once a day - in the morning during a meal. The tablet should be swallowed without chewing.
As with other medications for the treatment of psychiatric disorders, abrupt withdrawal of the drug should be avoided.
Major depressive disorder. The recommended daily dose is 20 mg. Usually the condition begins to improve after a week, but sometimes improvement is not seen until the second week of treatment.
As with all other antidepressants, the dose should be carefully titrated individually during the first 3–4 weeks of treatment and then adjusted according to clinical response.
For the treatment of some patients with insufficient response to the 20 mg dose, an increase in dose may be necessary. This should be done gradually, increasing the dose by 10 mg (up to a maximum of 50 mg per day) depending on the clinical effectiveness of the treatment. The course of treatment of patients with depression should be long enough, at least 6 months, to ensure the elimination of symptoms.
Obsessive-compulsive disorder. The recommended daily dose is 40 mg. Treatment should be started with a dose of 20 mg per day and then gradually increased by 10 mg per day to the recommended dose. In some patients, improvement is observed only when using the maximum dose of 60 mg per day. The course of treatment for obsessive-compulsive disorder should be long enough to ensure the elimination of symptoms. This period may last several months or even longer.
Panic disorder. The recommended dose is 40 mg per day. Treatment should be initiated at a dose of 10 mg per day, then increased by 10 mg weekly, depending on the clinical response. Some patients may only improve with a maximum dose of 60 mg per day.
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. Long-term use of the drug should be reviewed periodically.
Generalized anxiety disorder. The recommended dose is 20 mg per day. In case of insufficient efficacy with 20 mg, the dose can be gradually increased by 10 mg per day, depending on the clinical effect, up to 50 mg per day. Long-term use of the drug should be reviewed periodically.
Post-traumatic stress disorder. The recommended dose is 20 mg per day. In case of insufficient efficacy with 20 mg, the dose can be gradually increased by 10 mg per day, depending on the clinical effect, up to 50 mg per day. Long-term use of the drug should be reviewed periodically.
Paroxetine Withdrawal
As with other drugs for the treatment of mental illness, abrupt withdrawal of the drug should be avoided. In clinical trials, a gradual dose reduction regimen was used, which included a reduction in the daily dose by 10 mg per day at intervals of 1 week. After reaching a dosage regimen of 20 mg per day, patients continued to take the drug at this dose for another week before completely withdrawing it. In the event of severe symptoms during dose reduction or after discontinuation of treatment, it is necessary to decide whether to resume 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 gradually increased to 40 mg daily. Increased 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: Paroxetine 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.
Children
Paroxetine is not indicated for the treatment of children.
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 have been observed.
All these effects in patients mostly passed without serious consequences even after the use of a dose of 2000 mg. Sometimes coma or changes in ECG parameters were observed, very rarely fatal cases were noted, but mainly in such cases Paroxetine was taken together with other psychotropic drugs, sometimes with alcohol.
Specific antidote unknown
Treatment of overdose should include general therapeutic measures, the same as for overdose with other antidepressants. Supportive treatment with monitoring of vital signs and careful observation of the patient is indicated.
Adverse reactions
The adverse reactions listed below are classified by system organ class and by frequency of occurrence. The frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000, including isolated reports).
Blood and lymphatic system
Uncommon: increased bleeding, mainly of the skin and mucous membranes (including ecchymoses and gynaecological bleeding). Very rare: thrombocytopenia.
Immune system
Very rare: severe and potentially fatal allergic reactions (including anaphylactoid reactions and angioedema).
Endocrine system
Very rare: syndrome due to inadequate secretion of antidiuretic hormone.
Metabolism and digestive disorders
Common: increased cholesterol levels, decreased appetite. Uncommon: there are reports of an altered glycemic profile in patients with diabetes mellitus (see section "Special instructions"). Rare: hyponatremia. Hyponatremia is mainly observed in elderly patients and is sometimes associated with the syndrome of inappropriate antidiuretic hormone secretion.
Mental disorders
Common: somnolence, insomnia, agitation, abnormal dreams (including nightmares). Uncommon: confusion, hallucinations. Rare: manic reactions, restlessness, depersonalisation, panic attacks, akathisia. Frequency not known: suicidal ideation.
