Instructions for Sempravil tablets 20 mg No. 30
Composition
active ingredient: paroxetine;
1 film-coated tablet contains paroxetine hydrochloride hemihydrate equivalent to paroxetine 20 mg;
excipients: calcium hydrogen phosphate dihydrate, sodium starch glycolate, magnesium stearate, coating for applying the shell "Opadry 1ZV58802 white"*.
* "Opadry 1ZV58802 white": hypromellose, titanium dioxide (E 171), macrogol, polysorbate 80.
Dosage form
Film-coated tablets.
Main physicochemical properties: oval-shaped tablets, white or almost white in color, film-coated, with a break line on one side and smooth on the other side.
Pharmacotherapeutic group
Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06A B05.
Pharmacological properties
Pharmacodynamics
Mechanism of action.
Paroxetine is a potent and selective inhibitor of 5-hydroxytryptamine (5-HT, serotonin) reuptake, and its antidepressant action and efficacy in the treatment of obsessive-compulsive disorder, social anxiety disorder/social phobia, generalized anxiety disorder, post-traumatic stress disorder, and panic disorder are thought to be due to specific inhibition of 5-HT reuptake by brain neurons.
Paroxetine differs in its chemical structure from tricyclic, tetracyclic, and other known antidepressants.
Paroxetine has low affinity for muscarinic cholinergic receptors and weak anticholinergic properties.
It, unlike tricyclic antidepressants, has a low affinity for alpha1-, alpha2- and beta-adrenergic receptors, dopamine (D2), 5-HT1-like, 5-HT2- and histamine (H1-) receptors. It is known that paroxetine does not have a depressive and hypotensive effect on the central nervous system, and also does not affect psychomotor function and does not enhance the depressive effect of ethanol.
Like other selective 5-HT reuptake inhibitors, paroxetine produces symptoms of overstimulation of 5-HT receptors when administered to animals previously treated with monoamine oxidase inhibitors (MAOIs) or tryptophan.
Behavioral and electroencephalographic (EEG) studies indicate that paroxetine is weakly activating at doses that are usually in excess of those required to inhibit 5-HT uptake. The activating properties are not "amphetamine-like" in nature.
When administered to healthy volunteers, paroxetine had no effect on the cardiovascular system and did not cause clinically significant changes in blood pressure, heart rate, or other electrocardiographic (ECG) parameters.
Paroxetine, unlike antidepressants that inhibit norepinephrine uptake, has a significantly reduced ability to inhibit the antihypertensive effects of guanethidine.
In the treatment of depressive disorders, paroxetine exhibits efficacy comparable to standard antidepressants.
There is also some evidence that paroxetine may have therapeutic value for patients who do not have a clinical response to standard therapy.
Taking paroxetine in the morning does not affect sleep quality or duration. In addition, patients are more likely to experience improved sleep as they respond to paroxetine therapy.
Pharmacokinetics
Absorption.
After oral administration, it is rapidly absorbed and undergoes transformation in the liver. Due to the breakdown of the drug in the liver, the amount of paroxetine circulating in the blood is less than the amount absorbed in 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.
Steady-state blood concentrations are achieved 7–14 days after the start of treatment, and during subsequent long-term treatment, the pharmacokinetics of the drug almost does not change.
Distribution.
Paroxetine is widely distributed in body tissues, and the values of 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.
No correlation was found between the concentration of paroxetine in blood plasma and the clinical effect (efficacy and adverse reactions).
Metabolism.
The major metabolites of paroxetine are polar and conjugated oxidation and methylation products that are rapidly excreted from the body. Given their relative lack of pharmacological activity, they are unlikely to contribute to the therapeutic effects of paroxetine.
Metabolism does not disrupt the selective action of paroxetine on 5-HT neuronal uptake.
Approximately 64% of the administered dose of paroxetine is excreted in the urine, with less than 2% of the dose excreted unchanged. Approximately 36% of the dose is excreted in the faeces, probably in the bile, of which less than 1% of the dose is unchanged paroxetine. Thus, paroxetine is almost entirely eliminated by metabolism.
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.
Special patient groups.
Elderly patients and patients with renal/hepatic insufficiency.
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
For treatment:
major depressive disorder;
obsessive-compulsive disorder;
panic disorder with or without concomitant agoraphobia;
social anxiety disorders/social phobias;
generalized anxiety disorder;
post-traumatic stress disorder.
Contraindication
Hypersensitivity to paroxetine or to any other component of the drug.
Combination of paroxetine with monoamine oxidase inhibitors (MAOIs): In exceptional cases, linezolid (an antibiotic that is a reversible non-selective MAOI) may be administered in combination with paroxetine, provided that facilities are available for close observation for symptoms of serotonin syndrome and monitoring of blood pressure (see section 4.5).
Treatment with paroxetine can be started:
two weeks after stopping irreversible MAO inhibitors or
at least 24 hours after stopping reversible MAO inhibitors, for example: moclobemide, linezolid, methylthioninium chloride (methylene blue).
There should be an interval of at least one week between stopping paroxetine and starting any MAOI.
Combination of paroxetine with thioridazine - As with other drugs that inhibit the hepatic enzyme CYP450 2D6, paroxetine may increase plasma levels of thioridazine (see section 4.5). Use of thioridazine alone may result in QTc prolongation with associated serious ventricular arrhythmias such as torsades de pointes and sudden death.
Combination of paroxetine 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 (SSRIs), concomitant use with serotonergic drugs may lead to a 5-HT-associated effect (serotonin syndrome - see section 4.4). Paroxetine should be used with caution and with careful clinical monitoring of the patient when combined with serotonergic drugs such as L-tryptophan, triptans, tramadol, linezolid, methylthioninium chloride (methylene blue), SSRIs, lithium, pethidine, buprenorphine and St. John's wort (Hypericum perforatum). Caution is also advised with fentanyl, which is used during general anesthesia or for the treatment of chronic pain. Concomitant use of paroxetine and MAO inhibitors is contraindicated due to the risk of serotonin syndrome (see section 4.4).
Pimozide.
An increase in pimozide levels (on average 2.5-fold) was demonstrated in a study of the co-administration of a single low dose of pimozide (2 mg) and paroxetine (60 mg). This was explained by the known inhibitory properties of paroxetine on CYP2D6. 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, paroxetine should be administered at the lowest effective dose possible.
When used concomitantly with enzyme-inducing drugs (carbamazepine, rifampicin, phenobarbital, phenytoin), there is no need to change the initial dose of paroxetine. The dose of paroxetine should be adjusted (after initiation of treatment or after discontinuation of the enzyme inducer) 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.
Co-administration of fosamprenavir/ritonavir (700/100 mg twice daily) with paroxetine (20 mg daily) for 10 days in healthy volunteers significantly (approximately 55%) decreased plasma levels of paroxetine. Plasma fosamprenavir/ritonavir levels during co-administration with paroxetine were similar to control values in other studies, indicating that paroxetine had no significant effect on the metabolism of fosamprenavir/ritonavir. There are no data on the effect of long-term (>10 days) co-administration of paroxetine and fosamprenavir/ritonavir.
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 concomitantly 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., clomipramine, nortriptyline, and desipramine), phenothiazine neuroleptics (e.g., perphenazine and thioridazine, see section 4.3), risperidone, atomoxetine, some type 1c antiarrhythmics (e.g., propafenone and flecainide), and metoprolol. The combination of paroxetine with metoprolol in heart failure is not recommended due to the narrow therapeutic index of metoprolol in this indication.
A pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen has been reported in the scientific literature, showing a 65-75% decrease in plasma levels of one of the most active forms of tamoxifen, endoxifen. Some studies have shown a decrease in the efficacy of tamoxifen when used concomitantly with certain SSRI antidepressants. Since a decrease in the effect of tamoxifen cannot be excluded, concomitant use with potent CYP2D6 inhibitors (including paroxetine) should be avoided if possible (see section 4.4).
Alcohol.
As with other psychotropic drugs, patients should be advised to avoid alcohol while taking paroxetine.
Oral anticoagulants.
A pharmacodynamic interaction may occur between paroxetine and oral anticoagulants. Concomitant use of paroxetine and oral anticoagulants may lead to increased anticoagulant activity and risk of bleeding. Therefore, paroxetine should be prescribed with caution to patients treated with oral anticoagulants (see section 4.4).
Nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, and antiplatelet agents.
When NSAIDs/acetylsalicylic acid are used concomitantly with paroxetine, a pharmacodynamic interaction may occur, increasing the risk of bleeding. Paroxetine should be administered with caution in combination with drugs that affect platelet function or increase the risk of bleeding (see section 4.4).
Caution is advised when SSRIs are used concomitantly with 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, NSAIDs, cyclooxygenase-2 [COX-2] inhibitors) in patients with blood disorders or conditions that may predispose to 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
It is recommended that paroxetine treatment be initiated with caution two weeks after discontinuation of an irreversible MAOI or 24 hours after discontinuation of a reversible MAOI. The dosage of paroxetine should be increased gradually until the optimal response is achieved (see sections 4.3 and 4.5).
Children
Paroxetine should not be used in the treatment of children and adolescents (under 18 years of age). Suicide-related behaviour (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were observed more frequently in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless made, the patient should be closely monitored for the appearance of suicidal symptoms.
Suicide/suicidal thoughts or worsening of condition.
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicidality). This risk persists until significant remission occurs. As improvement may not occur within the first few weeks of treatment or even later, close monitoring is necessary until the patient's condition improves. Based on available clinical experience, the risk of suicide is increased in the early stages of recovery.
Other psychiatric conditions for which paroxetine is prescribed may also be associated with an increased risk of suicide. In addition, these conditions may accompany major depressive disorder. Therefore, the same precautions should be observed in the treatment of major depressive disorder as in the treatment of other psychiatric disorders.
Because the risk of suicidal thoughts or suicide attempts is greater in patients with a history of suicidality or with significant suicidal ideation prior to initiation of treatment, 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 in patients under 25 years of age treated with antidepressants compared with placebo (see section 5.1).
Close observation of patients, especially those at high risk, is necessary when initiating treatment with paroxetine or when changing its dosage. Patients (and their caregivers) should be warned about the need to monitor for any signs of worsening of the condition, suicidal behavior/thoughts, and unusual changes in behavior. If such symptoms appear, they should seek medical advice immediately.
Akathisia/psychomotor restlessness.
The use of paroxetine has been 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 condition is most likely to occur during the first weeks of treatment. In patients who experience these symptoms, increasing the dose may be harmful.
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.
As with other antidepressants, paroxetine should be used with caution in patients with a history of mania. Paroxetine should be discontinued if the patient develops a manic phase.
Renal/liver dysfunction.
Caution is recommended when using the drug in patients with severe renal or hepatic impairment (see section "Method of administration and dosage").
Diabetes.
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. Clinical studies indicate that an increase in blood glucose levels may occur with concomitant treatment with paroxetine and pravastatin (see section "Interaction with other medicinal products and other forms of interaction").
Epilepsy.
As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.
Convulsive attacks.
Among patients taking paroxetine, seizures occur with a frequency of less than 0.1%. If seizures occur, treatment with the drug should be discontinued.
Electroconvulsive therapy (ECT).
Experience with the concomitant use of paroxetine and ECT is limited.
Glaucoma.
Paroxetine, like other serotonin reuptake inhibitors, may cause mydriasis and should be used with caution in patients with current or history of angle-closure glaucoma.
Heart disease.
When treating patients with concomitant heart disease, the usual precautions should be taken.
Hyponatremia.
Bleeding.
Skin bleeding, such as ecchymoses and purpura, has been reported following treatment with SSRIs. Other bleeding manifestations, including gastrointestinal and gynaecological bleeding, have been reported. Elderly patients may be at increased risk of non-menstrual bleeding.
SSRIs/INRs increase the risk of postpartum hemorrhage (see sections “Use during pregnancy or lactation” and “Adverse reactions”).
Therefore, paroxetine should be used with caution in patients taking concomitant oral anticoagulants, drugs that affect platelet function, or other drugs that increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, NSAIDs, COX-2 inhibitors), as well as in patients with a history of frequent coagulopathies or diseases that may lead to bleeding (see section "Adverse reactions").
Interaction with tamoxifen.
Paroxetine, a potent CYP2D6 inhibitor, may decrease the concentration of endoxifen, one of the major active metabolites of tamoxifen. Therefore, paroxetine should be avoided during tamoxifen treatment (see section 4.5).
Bone fractures.
Epidemiological studies on the risk of bone fractures with the use of some antidepressants, including selective serotonin reuptake inhibitors, have shown an association with fractures. The risk occurs during treatment and is highest in the initial stages of therapy. When treating patients with paroxetine, the possibility of bone fractures should be taken into account.
Withdrawal symptoms observed when stopping paroxetine
Withdrawal symptoms are common when treatment is discontinued, particularly if the drug is discontinued abruptly (see section 4.8). In clinical trials in adults, adverse reactions to paroxetine treatment were reported in 30% of patients compared with 20% of patients on placebo. The occurrence of withdrawal symptoms is not the same as that seen in drug abuse or dependence.
The risk of developing withdrawal symptoms may depend on several factors, including the duration of therapy, dose, and rate of tapering.
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, palpitations, emotional lability, irritability and visual disturbances have been reported. These symptoms are generally mild to moderate in nature, although in some patients they may be very intense. 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 gradually reduced over a period of several weeks or months, depending on the individual patient (see section 4.2).
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.
Sodium.
This medicine contains less than 1 mmol (23 mg) sodium per tablet, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy.
Some epidemiological studies have suggested an increased risk of congenital malformations, particularly cardiovascular (e.g. atrial or ventricular septal defects), associated with the use of paroxetine during the first trimester of pregnancy. The mechanism is unknown. The data suggest that the risk of having a child with a cardiovascular defect following paroxetine exposure during pregnancy is less than 2/100 compared with the expected incidence of such defects of approximately 1/100 in the general population.
Paroxetine should be used during pregnancy only if clearly indicated. The prescribing physician should consider alternative treatment options for pregnant women or women planning to become pregnant. Abrupt discontinuation of the drug should be avoided during pregnancy (see sections 4.4 and 4.2).
According to studies, an increased risk of postpartum hemorrhage (less than 2-fold) was observed in women who took SSRIs/INRs in the month before childbirth (see sections “Special instructions for use” and “Adverse reactions”).
Symptoms that may occur in newborns after paroxetine use in late pregnancy include: respiratory distress, cyanosis, apnoea, seizures, temperature fluctuations, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, shaking, excitability, lethargy, persistent crying, somnolence and difficulty sleeping. These symptoms may be due to serotonergic effects or withdrawal symptoms. Some reports have described the symptoms as neonatal withdrawal symptoms. In most cases, they occur immediately or shortly (< 24 hours) after delivery.
Epidemiological studies have shown that the use of SSRIs during pregnancy, particularly in late pregnancy, has been associated with an increased risk of persistent pulmonary hypertension of the newborn. The observed risk is approximately 5 cases per 1,000 pregnancies. In the general population, there are one to two cases of persistent pulmonary hypertension of the newborn per 1,000 pregnancies.
Animal studies have shown reproductive toxicity, but do not indicate direct harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.
Breastfeeding period.
Small amounts of paroxetine are excreted in human milk. In published studies, serum concentrations of paroxetine in breastfed infants of women taking paroxetine were below the limit of detection (< 2 ng/ml) or very low (< 4 ng/ml), and no evidence of drug effects in these infants was observed. Since no effects are expected, breastfeeding may be considered.
Fertility.
Preclinical and in vitro data suggest that paroxetine may affect sperm quality. However, reports of effects of some SSRIs (including paroxetine) on sperm quality in men who have used them suggest that these effects are reversible. Effects on human fertility have not been observed to date.
Ability to influence reaction speed when driving vehicles or other mechanisms
Clinical experience suggests 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, however, the combined use of paroxetine and alcohol is not recommended.
Method of administration and doses
Major depressive disorder.
The recommended dose is 20 mg per day. Patients generally begin to improve within a week, but may not become apparent until the second week of therapy.
As with all antidepressants, the dose of paroxetine should be carefully individualized and adjusted accordingly during the first 3–4 weeks of therapy, and then as clinically indicated.
If the clinical effect of 20 mg is insufficient, the dose can be gradually increased (in 10 mg increments) to a maximum of 50 mg per day according to the patient's response.
Patients with depressive disorder should receive treatment for a long period (at least 6 months) to ensure resolution of symptoms.
Obsessive-compulsive disorder.
The recommended dose is 40 mg per day. Treatment should be initiated at 20 mg per day and increased by 10 mg per day weekly until the recommended dose is reached. If insufficient clinical response is observed after several weeks of taking the recommended dose, some patients may require a gradual increase in dose to a maximum of 60 mg per day.
The course of treatment for patients with obsessive-compulsive disorder should be sufficient to ensure resolution of symptoms. This period may last several months or even longer (see section "Pharmacodynamics").
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, to the recommended dose. If insufficient clinical effect is observed after several weeks of taking the recommended dose, some patients may require a gradual increase in dose to a maximum of 60 mg per day.
The course of treatment for patients with panic disorder should be sufficient to ensure resolution of symptoms. This period may last several months or even longer (see section 5.2).
Social anxiety disorders/social phobias.
The recommended dose is 20 mg per day. If after several weeks of taking the recommended dose there is insufficient clinical effect, some patients may need to gradually increase the dose by 10 mg to a maximum of 50 mg/day. Long-term use should be evaluated regularly (see section "Pharmacodynamics").
Generalized anxiety disorder.
The recommended dose is 20 mg per day. For some patients for whom 20 mg is not effective enough, the dose may be gradually increased by 10 mg per day, depending on the clinical effect, up to 50 mg per day. Long-term use should be regularly evaluated (see section "Pharmacodynamics").
The recommended dose is 20 mg/day. For some patients for whom 20 mg is not effective enough, the dose may be increased gradually by 10 mg/day, depending on the clinical response, up to 50 mg/day. Long-term use should be evaluated regularly (see section 5.1).
Withdrawal symptoms observed after stopping paroxetine.
Abrupt discontinuation should be avoided (see sections 4.4 and 4.8). In clinical trials, a gradual tapering regimen was used, involving a reduction in the daily dose by 10 mg/day at 1-week intervals. If severe symptoms occur during dose reduction or after discontinuation of treatment, resuming treatment at the previous dose should be considered.
Over time, you can continue to gradually reduce the dose.
Special patient groups.
Elderly patients.
Increased plasma concentrations of paroxetine are observed in elderly patients, but the range of concentrations is somewhat similar to that observed in younger patients. Treatment should be initiated at the adult starting dose. Some patients may require an increase in dose, but the maximum dose should not exceed 40 mg per day.
Renal/hepatic failure.
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.
Method of application.
It is recommended to take paroxetine once a day - in the morning with a meal.
The tablet should be swallowed without chewing.
Children
Paroxetine should not be used in children (under 18 years of age) because controlled clinical trials have associated paroxetine with an increased risk of suicidal behaviour and hostility. In addition, efficacy has not been adequately demonstrated in these trials. The safety and efficacy of the drug in children under 7 years of age have not been established.
Overdose
Symptoms.
In case of paroxetine overdose, in addition to the symptoms mentioned in the "Adverse Reactions" section, an increase in body temperature and involuntary muscle contractions have been observed.
All these effects in most patients 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 mostly in such cases paroxetine was used together with other psychotropic drugs or with alcohol.
Treatment.
Specific antidote is unknown.
Treatment of overdose should include general therapeutic measures, the same as for overdose with other antidepressants. Within a few hours after overdose, the use of 20-30 g of activated charcoal may be appropriate to reduce the absorption of paroxetine. Supportive therapy with monitoring of vital signs and close observation of the patient in a hospital setting is indicated. Treatment should be selected depending on the clinical condition of the patient.
Side effects
Some of the adverse reactions listed below may decrease in intensity and frequency with continued treatment and usually do not require discontinuation of therapy.
Adverse reactions are listed by system organ class and frequency. The frequency is defined as: 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); not known (cannot be estimated from the available data).
From the blood and lymphatic system.
Uncommon: increased bleeding, mainly of the skin and mucous membranes (including ecchymoses and gynecological bleeding).
Very rare: thrombocytopenia.
From the immune system.
Very rare: severe and potentially fatal
