Instructions for Trivonor tablets 20 mg No. 28
Composition
active ingredient: paroxetine;
1 tablet contains paroxetine mesylate 25.83, which is equivalent to paroxetine 20 mg;
excipients: calcium hydrogen phosphate, anhydrous, sodium starch glycolate, magnesium stearate;
shell composition: lactose monohydrate, hydroxypropylmethylcellulose, titanium dioxide (E 171), polyethylene glycol 4000, yellow iron oxide (E 172), red iron oxide (E 172).
Dosage form
Film-coated tablets.
main physicochemical properties: film-coated tablets, yellow to orange, oval or round in shape. The tablets are embossed with "POT 20" on one side. The tablets are scored on both sides.
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.
Paroxetine does not affect the activity of the cardiovascular system, 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.
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% of paroxetine excreted unchanged. 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 and then by systemic elimination of paroxetine. The average half-life is 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 plasma concentrations of the drug are achieved when using low doses.
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 adult volunteers.
Indication
Adults.
Major depressive disorder. Treatment of major depressive disorder.
Obsessive-compulsive disorder. Treatment of symptoms and prevention of relapses 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. Trivonor should not be used concomitantly with monoamine oxidase inhibitors (MAOIs), including linezolid, an antibiotic that is a reversible non-selective MAO inhibitor, and with methylthioninium chloride (methylene blue), and within 2 weeks of discontinuation of treatment with MAOIs.
Similarly, MAO inhibitors should not be used earlier than 2 weeks after stopping treatment with paroxetine (see section “Interaction with other medicinal products and other types of interactions”).
Trivonor should not be used in combination with thioridazine because, like other drugs that inhibit the hepatic enzyme CYP450 2D6, paroxetine may increase thioridazine levels (see section 4.5). Thioridazine may cause QT prolongation with associated severe ventricular arrhythmias (e.g. torsades de pointes) and sudden death.
Trivonor should not be prescribed 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 (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 when used with serotonergic drugs such as L-tryptophan, triptans, tramadol, other serotonin reuptake inhibitors, lithium, fentanyl and St. John's wort. 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 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 co-administered with enzyme-inhibiting drugs, it is recommended to use the lowest effective dose. When co-administered 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 subsequent 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 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 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).
In in vivo experiments, the combined use of paroxetine and terfenadine - a substrate for the CYP3A4 enzyme - when achieving a constant concentration in the blood was not accompanied by the 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 cannot be dangerous. It is known that during clinical studies it was found that the absorption or pharmacokinetics of paroxetine are not affected or almost not affected (i.e. do not require a change in dosage) by the following factors: food, antacids, digoxin, propranolol, alcohol. The drug Trivonor does not increase the impairment of mental and motor reactions caused by the action of alcohol, however, the use of 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 combination with medicinal products 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
Deterioration of clinical condition and risk of suicide.
Younger adult patients, particularly those with major depressive disorder, may be at increased risk of suicidal behavior while being treated with paroxetine. Patients with depressive disorders may experience worsening of their depressive symptoms and/or suicidal thoughts and behavior, whether or not they are taking antidepressants. This risk persists until significant remission occurs. The risk of suicide may be increased 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 associated with major depressive disorder. Patients with a history of suicidal behaviour and intention, 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 closely observed 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.
It should be understood that the appearance of some symptoms, such as agitation, akathisia or mania, may be related to both the course of the disease and the course of treatment (see section "Adverse reactions").
In patients with clinical worsening (including the development of new symptoms) and/or the emergence of suicidal thoughts/behavior, especially if these symptoms are severe, sudden in onset, or not previously observed in the patient, it is necessary to change the drug regimen up to and including its discontinuation.
Akathisia.
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. In the event of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations 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, treatment with paroxetine should be discontinued (since these symptoms are life-threatening) 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 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 of developing 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. 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.
Studies investigating the risk of bone fractures with some antidepressants, including SSRIs, have reported an association with fractures. The risk is present during treatment 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.
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, known clinical studies indicate that an increase in blood glucose levels may occur with concomitant treatment with paroxetine and pravastatin.
Epilepsy.
Trivonor, 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, Trivonor should be discontinued.
Electroconvulsive therapy.
There is only limited clinical experience with the use of paroxetine in combination with electroconvulsive therapy.
Glaucoma.
Trivonor, 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.
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.
Heart disease.
When treating patients with concomitant cardiac disease, the usual precautions should be observed.
Sexual dysfunction.
SSRIs may cause symptoms of sexual dysfunction (see section 4.8). In some cases, these symptoms have persisted after discontinuation of treatment.
The appearance of symptoms when a drug is discontinued is not analogous to the situation where addiction or dependence on a drug occurs when it 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, 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 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”). Important information about excipients.
This medicine contains 5.95 mg sodium per tablet, i.e. it is essentially sodium-free.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
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. Altered 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 prescribe paroxetine only if the expected benefit to the mother outweighs the potential risk to the fetus.
There have been reports of premature births in women treated with paroxetine or other SSRIs, although a causal relationship to the drug has not been established. Newborns should be examined if the pregnant woman continues to take paroxetine in the third trimester of pregnancy, as there have been reports of complications in newborns when the mother was treated 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, apnea, convulsions, temperature fluctuations, difficulty feeding, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, excitability, lethargy, constant crying and drowsiness. Sometimes these symptoms are associated with drug withdrawal. In most cases, they occur immediately or shortly (<24 hours) after delivery.
Studies have shown that the use of SSRIs (including paroxetine) in pregnant women, especially in late pregnancy, has been associated with an increased risk of persistent pulmonary hypertension in the newborn. In women who used SSRIs in late pregnancy, this risk was 4-5 times higher than in the general population.
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 breastfeeding 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
Experience with the use of paroxetine in clinical practice indicates that the 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.
Method of administration and doses
General recommendations.
The drug Trivonor 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.
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 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 (maximum 50* mg per day) depending on the clinical effectiveness of the treatment. Obsessive-compulsive disorder. The recommended dose is 40 mg per day. Treatment should be started with a dose of 20 mg and gradually increased by 10* mg per week. If necessary, the dose can 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 when taking 20 mg, the dose can be gradually increased by 10* mg per day, depending on the clinical effect, up to 50* mg per day.
Abolition of Trivandrum.
As with other drugs for the treatment of mental illness, abrupt withdrawal of the drug should be avoided. A gradual dose reduction 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. Trivonor 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 medications, paroxetine in the appropriate dosage.
Children.
Trivonor 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
Symptoms. In case of overdose with paroxetine, in addition to the symptoms mentioned in the section "Adverse reactions", an increase in body temperature, changes in blood pressure, involuntary muscle contractions, anxiety and tachycardia have been 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 have been observed, very rarely fatal outcomes have been noted, but mainly in such cases paroxetine was used together with other psychotropic drugs or with alcohol.
Specific antidote is unknown.
Treatment. Treatment of overdose should include general therapeutic measures, the same as for overdose with other antidepressants. Supportive therapy with monitoring of vital signs and close observation of the patient in a hospital setting is indicated.
Side effects
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), including isolated cases; frequency unknown (cannot be estimated from the available data).
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, restless legs syndrome; very rare - serotonin syndrome (may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, tachycardia and tremor). Extrapyramidal disorders, including orofacial dystonia, have been observed in patients with movement disorders or in patients treated with neuroleptics.
On the part of the organs of vision: common - blurred vision; uncommon - mydriasis (see section "Special instructions for use"); very rare - acute glaucoma.
On the part of the auditory organs: frequency unknown - ringing in the ears.
Cardiovascular system: uncommon - sinus tachycardia, postural hypotension, transient increase or decrease in blood pressure; rare - bradycardia. Respiratory system: common - yawning.
Gastrointestinal: very common - nausea; common - constipation, diarrhea, vomiting, dry mouth; very rare - gastrointestinal bleeding.
Hepatobiliary disorders: Rare: Elevated liver enzymes; Very rare: Liver disorders (such as hepatitis, sometimes with jaundice and/or liver failure). Elevated liver enzymes have been reported. Hepatic adverse reactions (such as hepatitis, sometimes with jaundice and/or liver failure) have also been reported very rarely. Discontinuation of paroxetine should be considered if liver function tests persist.
Skin and subcutaneous tissue disorders: common - increased sweating; uncommon - skin rash, itching; very rare - severe skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrosis), urticaria, photosensitivity reactions.
Urinary system: uncommon - urinary retention, urinary incontinence. Reproductive system: very common - sexual dysfunction; rare - hyperprolactinemia/galactorrhea, menstrual disorders (including menorrhagia, metrorrhagia, amenorrhea, delayed and irregular menstruation); very rare - priapism.
Musculoskeletal system: rarely - arthralgia, myalgia. Epidemiological studies, conducted mainly in patients over 50 years of age, indicate an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown.
General disorders: common - asthenia, weight gain; very rare - peripheral edema.
Symptoms caused by drug withdrawal: common - dizziness, sensory disturbances, sleep disorders, anxiety, headache; uncommon - agitation, nausea, tremor, confusion, increased sweating, diarrhea, emotional instability, visual disturbances, palpitations, agitation. As with other drugs for the treatment of psychiatric disorders, withdrawal of Trivonor (especially sudden) may lead to symptoms such as dizziness, sensory disturbances (including paresthesias, electric shock sensations and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, headache, tremor, confusion, diarrhea, increased sweating, increased heartbeat, agitation, emotional lability, visual disturbances. In most patients these symptoms are mild or moderate and resolve without treatment. There is no particular risk group for these symptoms, therefore, if it is necessary to discontinue treatment with paroxetine, the dose should be reduced gradually (see sections "Special instructions for use" and "Method of administration and dosage").
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions
