Paroxin
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Paroxin (Paroxin)
Composition:
Active substance: paroxetine hydrochloride hemihydrate;
One tablet contains paroxetine hydrochloride hemihydrate equivalent to 20 mg of paroxetine;
Excipients: calcium hydrogen phosphate dihydrate, sodium starch glycolate (type A), microcrystalline cellulose, magnesium stearate, Opadry® TF White coating (polyvinyl alcohol, calcium carbonate, polyethylene glycol/macrogol, talc).
Pharmaceutical form. Film-coated tablets.
Main physicochemical properties: white, film-coated, biconvex, round tablets with a break line on one side.
Pharmacotherapeutic group. Antidepressants. ATC code N06AB05.
Pharmacological Properties
Pharmacodynamics
Paroxetine is a potent selective inhibitor of the reuptake of 5-hydroxytryptamine (5-HT, serotonin). Its antidepressant effect and efficacy in the treatment of obsessive-compulsive and panic disorders are due to specific inhibition of 5-hydroxytryptamine reuptake by brain neurons. Chemically, paroxetine differs from tricyclic, tetracyclic, and other known antidepressants.
The drug has low affinity for muscarinic cholinergic receptors. Unlike tricyclic antidepressants, it has minimal affinity for alpha1-, alpha2-, and beta-adrenergic receptors, dopaminergic (D2) receptors, 5-HT1-like, 5-HT2-, and histamine (H1) receptors; it does not affect psychomotor function and does not potentiate the depressant effect of ethanol.
The medicinal product Paroxetine does not affect cardiovascular system activity and does not cause clinically significant changes in blood pressure, heart rate, or ECG parameters.
The medicinal product Paroxetine, unlike antidepressants that inhibit norepinephrine reuptake, has a much lesser effect on the antihypertensive action of guanethidine.
Pharmacokinetics
After oral administration, paroxetine is rapidly absorbed and undergoes hepatic transformation.
The main metabolites of paroxetine are polar and conjugated products of oxidation and methylation, which are rapidly eliminated from the body.
Approximately 64% of the administered dose of paroxetine is excreted in the urine, with less than 2% excreted unchanged. About 36% of the administered dose is excreted in the feces as metabolites.
Paroxetine metabolites are eliminated in two phases—first via first-pass hepatic metabolism, and then via systemic elimination of paroxetine.
The elimination half-life averages approximately 1 day.
Steady-state plasma concentration is achieved within 7–14 days after initiation of treatment. During prolonged therapy, the pharmacokinetics of the drug remain almost unchanged.
No correlation has been found between plasma paroxetine concentration and clinical effect (efficacy and adverse reactions).
Due to hepatic breakdown, the amount of paroxetine circulating in the blood is lower than the amount absorbed in the gastrointestinal tract. With increasing single doses or repeated dosing, partial saturation of the first-pass hepatic metabolic pathway occurs, resulting in reduced plasma clearance. This leads to a disproportionate increase in plasma paroxetine concentration and changes in pharmacokinetic parameters, exhibiting nonlinear kinetics. However, this nonlinearity is generally minor and is observed only in patients who achieve low plasma concentrations of the drug when low doses are administered.
Paroxetine is widely distributed in body tissues. Calculated pharmacokinetic parameters indicate that only 1% of the administered dose remains in the plasma.
At therapeutic concentrations, approximately 95% of paroxetine is protein-bound in plasma.
In elderly patients and in patients with renal or hepatic impairment, increased plasma concentrations of paroxetine are observed, but these remain within the range of fluctuations observed in healthy adult volunteers.
Clinical characteristics.
Indications.
Adults
Major depressive disorder. Treatment of major depressive disorder.
Obsessive-compulsive disorder. Treatment of symptoms and prevention of relapse in obsessive-compulsive disorder.
Panic disorder. Treatment of symptoms and prevention of relapse in panic disorder with or without agoraphobia.
Social phobias/social anxiety disorders. Treatment of social phobias/social anxiety disorders.
Generalized anxiety disorder. Treatment of symptoms and prevention of relapse in generalized anxiety disorder.
Post-traumatic stress disorder. Treatment of post-traumatic stress disorder.
Contraindications.
Hypersensitivity to paroxetine or to any of the other components of the medicinal product.
The medicinal product Paroxetine must not be used concomitantly with monoamine oxidase inhibitors (MAOIs), including linezolid—an antibiotic that is a reversible non-selective MAO inhibitor—and methylene blue (methylthioninium chloride), or within 2 weeks of discontinuing MAOI therapy.
Similarly, MAOIs must not be initiated earlier than 2 weeks after discontinuation of paroxetine (see section "Interaction with other medicinal products and other forms of interaction").
The product must not be used in combination with thioridazine, since, like other agents that inhibit the hepatic enzyme CYP450 2D6, paroxetine may increase thioridazine levels (see section "Interaction with other medicinal products and other forms of interaction"). Administration of thioridazine may lead to QT interval prolongation with associated severe ventricular arrhythmias (e.g., torsades de pointes) and sudden death. The medicinal product Paroxetine must not be prescribed in combination with pimozide (see section "Interaction with other medicinal products and other forms of interaction").
Interaction with other medicinal products and other forms of interaction.
Serotonergic agents
As with other selective serotonin reuptake inhibitors (SSRIs), concomitant use with serotonergic agents may lead to a 5-HT-related effect (serotonin syndrome).
Paroxetine should be used with caution together with serotonergic agents such as L-tryptophan, triptans, tramadol, other serotonin reuptake inhibitors, lithium, fentanyl, buprenorphine, and the herbal preparation Hypericum perforatum (St. John's wort), and patients must be closely monitored. Concomitant use of paroxetine and MAO inhibitors, including linezolid—an antibiotic that is also a reversible non-selective MAO inhibitor—and methylene blue (methylthioninium chloride) is contraindicated (see section "Contraindications").
Pimozide
Data from a study on the concomitant administration of a single low dose of pimozide (2 mg) and paroxetine showed an increase in pimozide levels. This was explained by the known CYP2D6 inhibitory properties of paroxetine. Due to the narrow therapeutic index of pimozide and its ability to prolong the QT interval, concomitant use of pimozide and paroxetine is contraindicated (see section "Contraindications").
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 drugs that inhibit enzymes, the lowest effective doses should be prescribed. When used concomitantly with enzyme-inducing drugs (carbamazepine, rifampicin, phenobarbital, phenytoin), no change in the initial dose of paroxetine is required. Dose adjustments during continued treatment should be made according to clinical response (tolerability and efficacy).
Neuromuscular blockers
SSRIs may reduce plasma cholinesterase activity, leading to prolonged neuromuscular blocking effects of mivacurium and succinylcholine.
Fosamprenavir/ritonavir
Concomitant use of fosamprenavir/ritonavir with paroxetine significantly reduces plasma levels of paroxetine. Dose adjustments during continued treatment should be based on clinical response (tolerability and efficacy).
Procyclidine
Daily administration of paroxetine significantly increases serum procyclidine levels. If anticholinergic effects occur, the dose of procyclidine should be reduced.
Anticonvulsants
Carbamazepine, phenytoin, sodium valproate. No effect on the pharmacokinetics/pharmacodynamics of the drug has been observed in epileptic patients when used concomitantly with these agents.
Paroxetine's ability to inhibit the CYP2D6 enzyme
Paroxetine, like other serotonin reuptake inhibitor antidepressants, inhibits the activity of the CYP2D6 enzyme of the cytochrome P450 system. Inhibition of CYP2D6 may lead to increased plasma concentrations of concomitantly administered drugs metabolized by this enzyme. These include certain tricyclic antidepressants (e.g., amitriptyline, nortriptyline, imipramine, and desipramine), phenothiazine neuroleptics (e.g., perphenazine and thioridazine), risperidone, atomoxetine, certain class 1c antiarrhythmics (e.g., propafenone and flecainide), and metoprolol.
Tamoxifen has an important active metabolite, endoxifen, produced by CYP2D6, which is a key component of tamoxifen's efficacy. Irreversible inhibition of CYP2D6 by paroxetine leads to reduced plasma concentrations of endoxifen (see section "Special precautions for use").
CYP3A4
In in vivo experiments, concomitant administration of paroxetine and terfenadine—a substrate of the CYP3A4 enzyme—at steady-state plasma concentrations did not result in any effect of paroxetine on the pharmacokinetics of terfenadine. Similarly, in vivo studies on interaction did not reveal any effect of the drug on the pharmacokinetics of alprazolam or vice versa. Concurrent administration of paroxetine with terfenadine, alprazolam, and other drugs that are substrates of CYP3A4 is not expected to be hazardous.
It is known from clinical studies that factors such as food, antacids, digoxin, propranolol, and alcohol have no or minimal effect on the absorption or pharmacokinetics of paroxetine (i.e., dose adjustment is not required).
The medicinal product Paroxetine does not potentiate the cognitive and motor impairments caused by alcohol; however, consumption of alcoholic beverages during paroxetine treatment is not recommended.
Oral anticoagulants
When oral anticoagulants and paroxetine are used concomitantly, a pharmacodynamic interaction may occur, potentially increasing anticoagulant activity and the risk of bleeding. Therefore, paroxetine should be prescribed with caution to patients receiving oral anticoagulants.
Non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and antiplatelet agents
When non-steroidal anti-inflammatory drugs/acetylsalicylic acid and paroxetine are used concomitantly, a pharmacodynamic interaction may occur, potentially increasing the risk of bleeding. Paroxetine should be prescribed with caution together with agents that affect platelet function or increase the risk of bleeding.
Pravastatin
The interaction between paroxetine and pravastatin observed in studies indicates that concomitant use of paroxetine and pravastatin may lead to increased blood glucose levels. Diabetic patients receiving both paroxetine and pravastatin may require dose adjustments of oral hypoglycemic agents and/or insulin (see section "Special precautions for use").
Special precautions for use.
Children and adolescents
Treatment with antidepressants is associated with an increased risk of suicidal behaviour and thoughts in children and adolescents with major depressive and other psychiatric disorders. Clinical trial data have shown that adverse effects related to suicidality (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behaviour, and irritability) occur more frequently in children and adolescents treated with paroxetine compared to placebo (see section "Adverse reactions"). There are no data on the safety of the drug in children and adolescents with respect to growth, development, cognitive, and behavioural characteristics.
Worsening of clinical condition and suicide risk in adults
Young adult patients, particularly those with major depressive disorders, may have an increased risk of suicidal behaviour during treatment with paroxetine. Data from placebo-controlled clinical trials in adults with psychiatric disorders have shown that young adults (approximately 18–24 years) had a higher incidence of suicidal behaviour compared to those in the placebo group (17 out of 776 (2.19%) versus 5 out of 542 (0.92%)), although this difference was not statistically significant. No such increase in risk was observed in older patient groups (25–64 years and over 65 years). In patients with major depressive disorders (of any age) treated with paroxetine, a statistically significant increase in the frequency of suicidal behaviour was observed compared to the placebo group (11 out of 3455 (0.32%) versus 1 out of 1978 (0.05%); all cases were suicide attempts). However, the majority of these attempts (8 out of 11) occurred in young adult patients aged 18–30 years. These data from major depressive disorder treatment suggest that the higher risk of such complications observed in younger psychiatric patients may extend to patients up to 24 years of age.
In patients with depressive disorders, symptoms of depression and/or emergence of suicidal thoughts and behaviour (suicidality) may worsen regardless of whether they are taking antidepressants. This risk persists until significant remission occurs. Clinical experience with all antidepressant treatments indicates that the risk of suicide may increase during the early stages of recovery.
Other psychiatric disorders for which paroxetine is prescribed may also be associated with an increased risk of suicidal behaviour, and such disorders may coexist with major depressive disorders. Additionally, patients with a history of suicidal behaviour and corresponding intentions, younger patients, and those with persistent suicidal ideation prior to the start of treatment represent a high-risk group for suicide attempts and suicidal thoughts. All patients should be closely monitored for worsening of their clinical condition (including the emergence of new symptoms) and suicidal behaviour during treatment, especially at the beginning of treatment or during dose adjustments (both increases and decreases). Patients (and caregivers) should be warned about the need for continuous monitoring for any worsening of condition (including new symptoms) and/or emergence of suicidal ideation/behaviour or thoughts of self-harm, and advised to seek immediate medical attention if such symptoms occur.
It should be understood that the emergence of certain symptoms such as agitation or akathisia or mania may be related to either the underlying disease or the course of treatment (see "Akathisia", "Mania and bipolar disorder" below, section "Adverse reactions").
Consideration should be given to modifying the therapeutic regimen, including discontinuation of the drug, in patients whose condition worsens clinically (including the emergence of new symptoms) and/or who develop suicidal thoughts/behaviour, particularly if these symptoms are severe, sudden in onset, or not part of the patient's previous symptom complex.
Akathisia
Rarely, the use of paroxetine or other SSRIs may be associated with the development of akathisia—a condition characterized by inner restlessness and psychomotor agitation, such as an inability to sit or stand still, combined with subjective feelings of discomfort. The likelihood of occurrence is greatest during the first weeks of treatment.
Serotonin syndrome/neuroleptic malignant syndrome
In isolated cases, treatment with paroxetine may be associated with the development of serotonin syndrome or symptoms typical of neuroleptic malignant syndrome, especially when used concomitantly with other serotonergic and/or neuroleptic agents. Since these syndromes may lead to life-threatening conditions, treatment with paroxetine should be discontinued if such symptoms occur (characterized by a combination of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs, and altered mental status including confusion, irritability, extreme agitation progressing to delirium and coma), and supportive symptomatic therapy should be initiated. Paroxetine should not be used in combination with serotonergic precursors (such as L-tryptophan, 5-hydroxytryptophan) due to the risk of serotonin syndrome (see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").
Mania and bipolar disorders
A major depressive episode may be the initial manifestation of bipolar disorder. It is generally accepted (although not confirmed by data from controlled clinical trials) that treating such episodes with antidepressants alone may increase the likelihood of triggering mixed/mania episodes in patients at increased risk of developing bipolar disorder. Before initiating antidepressant treatment, patients should be carefully evaluated for any risk of developing bipolar disorder. This evaluation should include a detailed review of the patient's medical history, including any history of suicide attempts, bipolar disorders, or depression in family members. It should be noted that paroxetine is not indicated for the treatment of depression in bipolar disorder. As with other antidepressants, paroxetine should be used cautiously in patients with a history of manic episodes.
Tamoxifen
Studies have shown that the efficacy of tamoxifen, measured by the risk of breast cancer recurrence or death, may be reduced when used concomitantly with paroxetine, as paroxetine is a potent irreversible inhibitor of CYP2D6 (see section "Interaction with other medicinal products and other forms of interaction"). This risk increases with longer duration of concomitant use. In patients being treated for breast cancer with tamoxifen, an alternative antidepressant with minimal or no CYP2D6 inhibition should be considered.
Bone fractures
Epidemiological studies investigating the risk of bone fractures associated with certain antidepressants, including SSRIs, have reported an association with fractures. The risk occurs during treatment and is highest in the initial stages of therapy. The potential for bone fractures should be considered when treating patients with paroxetine.
Monoamine oxidase inhibitors (MAOIs)
Treatment with paroxetine should be initiated cautiously, not earlier than 2 weeks after discontinuation of MAO inhibitors; the dose should be increased gradually until optimal response is achieved.
Renal/hepatic impairment
Paroxetine should be used with caution in patients with severe renal or hepatic impairment.
Diabetes mellitus
In patients with diabetes mellitus, treatment with serotonin reuptake inhibitors may alter glycaemic control, necessitating adjustment of insulin and/or oral hypoglycaemic agent doses. Additionally, clinical studies indicate that increased blood glucose levels may occur when paroxetine is used concomitantly with pravastatin.
Epilepsy
Paroxetine, like other antidepressants, should be used cautiously in patients with epilepsy.
Seizures
The overall incidence of seizures in patients treated with paroxetine is less than 0.1%. If seizures occur during treatment, paroxetine should be discontinued.
Electroconvulsive therapy (ECT)
There is only limited clinical experience with the use of paroxetine in combination with electroconvulsive therapy.
Glaucoma
The medicinal product Paroxin, like other serotonin reuptake inhibitors, may cause mydriasis and should therefore be used cautiously in patients with closed-angle glaucoma.
Hyponatraemia
Cases of hyponatraemia have occasionally been reported, mostly in elderly patients. In most cases, signs of hyponatraemia resolve after discontinuation of paroxetine.
Haemorrhage
After treatment with paroxetine, bleeding events have been observed in the skin and mucous membranes (including gastrointestinal and gynaecological bleeding). Therefore, paroxetine should be used cautiously in patients who are concurrently receiving medications with an increased risk of bleeding, as well as in patients with a history of frequent bleeding or predisposition to bleeding. Elderly patients may have an increased risk of non-menstrual bleeding.
SSRIs/SSNIs may increase the risk of postpartum haemorrhage (see sections "Use during pregnancy or breastfeeding", "Adverse reactions").
Cardiac disorders
Standard precautions should be observed when treating patients with concomitant cardiac disease.
Symptoms observed upon discontinuation of paroxetine
Clinical trial data indicate that adverse reactions upon discontinuation of paroxetine occurred in 30% of adult patients compared to 20% of those receiving placebo. The emergence of discontinuation symptoms does not indicate drug dependence or addiction.
Reported symptoms include dizziness, sensory disturbances (including paraesthesia, electric shock sensations, and tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, tremor, confusion, sweating, headache, and diarrhoea. Generally, these symptoms are mild to moderate in severity, although they may be more intense in some patients. They typically occur within the first few days after discontinuation, although isolated cases have been reported in patients who accidentally missed a single dose. These symptoms usually resolve spontaneously within 2 weeks, although in some patients the process may be prolonged (2–3 months or longer). Therefore, it is recommended that paroxetine be tapered gradually over several weeks or months, depending on individual patient characteristics (see section "Dosage and administration").
Symptoms observed in children and adolescents upon discontinuation of paroxetine
Clinical trial data indicate that adverse reactions upon discontinuation of paroxetine occurred in 32% of children and adolescents compared to 24% in the placebo group. After discontinuation of paroxetine, the following adverse effects occurred (with an incidence of at least 2% and at least twice that of the placebo group): emotional lability (including suicidal ideation, suicide attempts, mood swings, and tearfulness), nervousness, dizziness, nausea, and abdominal pain (see section "Adverse reactions").
Sexual dysfunction
SSRIs may cause symptoms of sexual dysfunction (see section "Adverse reactions"). In some cases, these symptoms persist after discontinuation of SSRIs.
Warning about excipients.
Sodium-containing compounds
One tablet contains less than 1 mmol (23 mg) of sodium, i.e., this medicinal product is considered essentially "sodium-free".
Use during pregnancy or breastfeeding.
Fertility
Clinical studies have demonstrated that SSRIs, including paroxetine, may affect sperm quality. These effects are considered reversible upon discontinuation of treatment. Changes in sperm parameters may affect fertility in some men.
Pregnancy
Teratogenic or embryotoxic effects of paroxetine have not been observed in animal studies.
Data from studies on pregnancy outcomes in women treated with antidepressants during the first trimester have reported an increased risk of congenital malformations, primarily cardiovascular (e.g., atrial or ventricular septal defects), associated with paroxetine use. According to these data, the risk of giving birth to an infant with a cardiovascular defect in women treated with paroxetine during pregnancy is approximately 1 in 50, compared to an expected risk of approximately 1 in 100 in the general population.
Physicians should consider the possibility of alternative treatments for pregnant women or women planning pregnancy and prescribe paroxetine only when the expected benefit to the mother outweighs the potential risk to the fetus. If a decision is made to discontinue treatment during pregnancy, additional information should be obtained from the relevant sections of the product's instructions regarding dosage and symptoms associated with discontinuation of paroxetine (see sections "Dosage and administration" and "Special precautions for use").
There have been reports of preterm delivery in women treated with paroxetine or other SSRIs, although a causal relationship with drug use has not been established.
Newborns should be monitored if the mother continued taking paroxetine during the third trimester, as there are reports of complications in neonates following maternal treatment with paroxetine or other SSRIs during this period, although a causal relationship has not been established. Reported effects include respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, arterial hypertension, hypotension, hyperreflexia, tremor, irritability, lethargy, persistent crying, and somnolence. In some reports, symptoms were described as neonatal withdrawal syndrome. In most cases, symptoms occur immediately or shortly (<24 hours) after birth.
Data from studies indicate that the use of SSRIs (including paroxetine) during pregnancy, particularly in late pregnancy, is associated with an increased risk of persistent pulmonary hypertension in the newborn. In women who used serotonin reuptake inhibitors during late pregnancy, this risk was increased 4–5 times compared to the general patient population (1–2 cases per 1000 pregnancies in the general population).
Observational data suggest an increased risk (less than 2-fold) of postpartum haemorrhage following exposure to SSRIs/SSNIs within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").
Lactation
A small amount of paroxetine is excreted in breast milk. No adverse effects of the drug on newborns have been observed; however, paroxetine should not be used during breastfeeding except when the expected benefit to the mother outweighs the potential risk to the infant.
Ability to influence reaction speed when driving or operating machinery.
Clinical experience with paroxetine 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 their ability to drive or operate machinery during treatment.
Paroxetine does not potentiate the impairment of mental and motor reactions caused by alcohol; however, concomitant use of paroxetine and alcohol is not recommended.
Method of Administration and Dosage
General Recommendations
The medicinal product Paroxetine should be administered orally, preferably once daily in the morning with food. The tablet should be swallowed whole, without chewing.
As with all other antidepressant agents, the dosage should be carefully individualized during the first 2–3 weeks of treatment and then adjusted according to clinical response.
The treatment course should be sufficiently long to ensure symptom resolution. This period may last several months when treating depression, and even longer for obsessive-compulsive disorder and panic disorder. As with other agents used in the treatment of psychiatric disorders, abrupt discontinuation of the drug should be avoided.
Major Depressive Disorder. The recommended dose is 20 mg once daily. Some patients may require dose increases. This should be done gradually, increasing the dose by 10* mg (up to a maximum of 50* mg daily) according to clinical efficacy.
Obsessive-Compulsive Disorder. The recommended dose is 40 mg once daily. Treatment should be initiated at a dose of 20 mg daily, with gradual weekly increases of 10* mg. If necessary, the dose may be increased up to a maximum of 60 mg daily.
Panic Disorder. The recommended dose is 40 mg once daily. Treatment should be initiated at a dose of 10* mg daily, with weekly increments of 10* mg according to clinical response. In some patients, improvement may only be achieved with the maximum dose of 60 mg daily.
To minimize the risk of symptom exacerbation, which is commonly observed at the beginning of treatment for panic disorder, it is recommended to initiate therapy with a low dose.
Social Anxiety Disorder/Social Phobia. The recommended dose is 20 mg once daily. For some patients, the dose may be gradually increased by 10* mg daily, according to clinical response, up to 50* mg daily. The interval between dose increases should be at least 1 week.
Generalized Anxiety Disorder. The recommended dose is 20 mg once daily. For patients with inadequate response to 20 mg, the dose may be gradually increased by 10* mg daily, according to clinical response, up to 50* mg daily.
Post-Traumatic Stress Disorder. The recommended dose is 20 mg once daily. For patients with inadequate response to 20 mg, the dose may be gradually increased by 10* mg daily, according to clinical response, up to 50* mg daily.
Discontinuation of Paroxetine
As with other medications used in the treatment of psychiatric disorders, abrupt discontinuation should be avoided. A gradual dose reduction regimen may be used, involving weekly reductions of 10* mg daily. After reaching a dosage regimen of 20 mg daily, patients should continue taking the medication at this dose for an additional week before complete discontinuation. If severe symptoms occur during dose reduction or after discontinuation, consideration should be given to resuming treatment at the previous dose. Dose reduction may then be continued at a slower rate.
Elderly Patients
Treatment should be initiated at the usual starting dose for adults, which may then be gradually increased up to 40 mg daily. Elevated plasma concentrations of paroxetine have been observed in elderly patients; however, the concentration range in this patient group overlaps with that observed in younger patients.
Children
The medicinal product Paroxetine is not indicated for the treatment of children.
Renal and Hepatic Impairment
In patients with severe renal impairment (creatinine clearance <30 mL/min) or hepatic impairment, increased plasma concentrations of paroxetine have been observed. Therefore, for such patients, the dose should be reduced to the lower end of the recommended dosage range.
* Administer paroxetine preparations at the corresponding dosage strength.
Children
The medicinal product Paroxetine is not indicated for the treatment of children. Controlled clinical studies have not demonstrated efficacy, and there is no supporting evidence for the use of paroxetine in the treatment of depression in pediatric patients.
Overdose
In cases of paroxetine overdose, in addition to the symptoms listed in the section "Adverse Reactions," the following have been observed: elevated body temperature, changes in blood pressure, involuntary muscle contractions, agitation, and tachycardia.
These effects usually resolve without serious consequences, even after ingestion of doses up to 2000 mg. Occasionally, coma or ECG changes have been observed; fatal outcomes are very rare and have generally occurred when paroxetine was taken concomitantly with other psychotropic agents or alcohol.
There is no specific antidote.
Management of overdose should include general supportive and symptomatic measures, as for overdose with other antidepressants. Supportive therapy with monitoring of vital functions and careful observation of the patient's condition in a hospital setting is indicated.
Side effects
The adverse reactions listed below are classified by system organ class and frequency of occurrence. 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), frequency not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:
Uncommon − leukopenia, increased bleeding tendency, predominantly of the skin and mucous membranes (including ecchymoses and gynecological bleeding); very rare − thrombocytopenia.
Immune system disorders:
Very rare − severe and potentially fatal allergic reactions (including anaphylactoid reactions and angioedema).
Endocrine system disorders:
Very rare − syndrome caused by inadequate secretion of antidiuretic hormone.
Metabolism and nutrition disorders:
Common − increased cholesterol levels, decreased appetite; uncommon − altered glycemic control has been reported in diabetic patients (see section "Special precautions"); rare − hyponatremia. Hyponatremia is mainly observed in elderly patients and is sometimes associated with the syndrome caused by inadequate 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 not known − suicidal ideation, suicidal behavior, and aggression. These symptoms may also be related to the underlying disease.
Nervous system disorders:
Common − dizziness, tremor, headache; uncommon − extrapyramidal disorders; rare − seizures, akathisia, restless legs syndrome; very rare − serotonin syndrome (may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, tachycardia, and tremor). Extrapyramidal disorders, including orofacial dystonia, are observed in patients with movement disorders or in those treated with neuroleptics.
Eye disorders:
Common − blurred vision; uncommon − mydriasis (see section "Special precautions"); very rare − acute glaucoma.
Ear and labyrinth disorders:
Frequency not known − tinnitus.
Cardiac disorders:
Uncommon − sinus tachycardia, postural hypotension, transient increase or decrease in blood pressure; rare − bradycardia.
Respiratory system disorders:
Common − yawning.
Gastrointestinal disorders:
Very common − nausea; common − constipation, diarrhea, vomiting, dry mouth; very rare − gastrointestinal bleeding; frequency not known − microscopic colitis.
Hepatobiliary disorders:
Rare − increased liver enzymes; very rare − hepatic disorders (such as hepatitis, sometimes with jaundice and/or hepatic failure). There have been reports of elevated liver enzymes. Very rare cases of hepatic adverse reactions (such as hepatitis, sometimes associated with jaundice and/or hepatic failure) have also been reported. Discontinuation of paroxetine should be considered if elevated liver function tests persist.
Skin and subcutaneous tissue disorders:
Common − increased sweating; uncommon − skin rash, pruritus; very rare − severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), urticaria, photosensitivity reactions.
Renal and urinary disorders:
Uncommon − urinary retention, urinary incontinence.
Reproductive system and breast disorders:
Very common − sexual dysfunction; rare − hyperprolactinemia/galactorrhea, menstrual disorders (including menorrhagia, metrorrhagia, amenorrhea, delayed and irregular menstruation); very rare − priapism; frequency not known − postpartum hemorrhage (pertains to the therapeutic group of SSRIs/SNRIs (see sections "Special precautions" and "Use during pregnancy or breastfeeding")).
Musculoskeletal and connective tissue disorders:
Rare − arthralgia, myalgia. Epidemiological studies, conducted primarily in patients aged 50 years and older, suggest an increased risk of bone fractures in patients treated with SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown.
General disorders:
Common − asthenia, weight gain; very rare − peripheral edema.
Symptoms associated with discontinuation of the drug:
Common − dizziness, sensory disturbances, sleep disturbances, anxiety, headache; uncommon − agitation, nausea, tremor, confusion, increased sweating, diarrhea, emotional lability, visual disturbances, palpitations, restlessness. As with other drugs used to treat psychiatric disorders, discontinuation of paroxetine (especially abrupt discontinuation) may lead to the emergence of symptoms such as dizziness, sensory disturbances (including paresthesia, electric shock sensations, and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, headache, tremor, confusion, diarrhea, increased sweating, palpitations, restlessness, emotional lability, and visual disturbances. In most patients, these symptoms are mild or moderate in severity and resolve without treatment. There is no specific risk group for the occurrence of these symptoms; therefore, if discontinuation of paroxetine treatment is necessary, the dose should be gradually reduced (see sections "Special precautions" and "Dosage and administration").
Adverse reactions reported in clinical trials involving pediatric patients.
In clinical trials involving pediatric patients, the following adverse effects were observed (occurring in at least 2% of patients and at twice the rate compared to placebo): emotional lability (including self-harm, suicidal thoughts, crying with suicidal threats, and mood changes), hostility, decreased appetite, tremor, increased sweating, hyperkinesia, and agitation. Suicidal thoughts and suicide attempts were observed primarily in adolescent patients with depressive disorders during clinical trials. Hostility was mainly observed in children with obsessive-compulsive disorder, particularly in children under 12 years of age.
During studies involving a gradual dose reduction regimen (reducing the daily dose by 10 mg per week until reaching 10 mg/day over one week) or after discontinuation of the drug, the following symptoms were observed (occurring in at least 2% of patients and at twice the rate compared to placebo): emotional lability, nervousness, dizziness, nausea, and abdominal pain (see section "Special precautions").
Shelf life.
3 years.
Storage conditions.
Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25 °C.
Packaging.
10 tablets in a blister; 3 or 6 blisters in a cardboard pack.
Prescription status.
By prescription only.
Manufacturer.
TOV "Pharma Start", Ukraine.
Manufacturer's address and location of business activity.
8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.
If adverse effects occur or if you have questions regarding the safety of using the medicinal product, please contact the Pharmacovigilance Department of TOV "ASINO UKRAINA" at: 8 Vatslava Havela Boulevard, Kyiv, 03124, Tel/Fax: +38 044 281 2333