Instructions Paroxin film-coated tablets 20 mg blister No. 30
Composition
active ingredient: paroxetine hydrochloride hemihydrate;
1 tablet contains paroxetine hydrochloride hemihydrate equivalent to paroxetine 20 mg;
excipients: calcium hydrogen phosphate dihydrate, sodium starch glycolate (type A), microcrystalline cellulose, magnesium stearate, coating for applying the shell Opadry II White (polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide (E 171)).
Dosage form
Film-coated tablets.
main physicochemical properties: round tablets, with a biconvex surface, with a score, covered with a white film coating.
Pharmacotherapeutic group
Antidepressants. ATX code N06A B05.
Pharmacological properties
Pharmacodynamics.
Paroxetine is a potent selective inhibitor of the uptake of 5-hydroxytryptamine (5-HT, serotonin) by brain neurons, which accounts for its antidepressant effect and efficacy.
Paroxetine is chemically different from tricyclic, tetracyclic, or any other currently 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; it does not cause clinically significant changes in blood pressure, heart rate and ECG parameters.
Paroxetine, unlike antidepressants that inhibit norepinephrine uptake, has a much smaller effect on the hypotensive effect of guanethidine.
The antidepressant effect of the drug is manifested after approximately 10 days of systemic administration. During treatment, a decrease in anxiety, depression, and sleep disorders is observed.
Pharmacokinetics.
After oral administration, it is rapidly absorbed and undergoes transformation in the liver.
The main metabolites of paroxetine are polar and conjugated oxidation and methylation products, which are rapidly excreted from the body.
Approximately 64% of an administered dose of paroxetine is excreted in the urine, with less than 2% excreted as unchanged paroxetine. Approximately 36% of an administered dose of paroxetine is excreted in the feces as metabolites.
Paroxetine metabolites are eliminated in 2 stages - first by first-pass metabolism through the liver, and then by systemic elimination of paroxetine.
The half-life is on average approximately 1 day.
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.
No correlation was found between paroxetine plasma concentrations and clinical effect (efficacy and adverse reactions).
Due to the breakdown of the drug in the liver, the amount of paroxetine circulating in the blood is less than the amount absorbed from the gastrointestinal tract. With an increase in a single dose or with repeated dosing, the effect of partial saturation of the metabolic pathway of the first pass through the liver occurs and a decrease in plasma clearance is observed. This leads to a disproportionate increase in the concentration of paroxetine in the blood plasma and changes in pharmacokinetic parameters with the appearance of a nonlinear relationship. However, such nonlinearity is mostly insignificant and is observed only in patients in whom low doses achieve a low concentration of the drug in the blood plasma.
Paroxetine is widely distributed in body tissues. Calculated pharmacokinetic parameters indicate that only 1% of the administered dose remains in the blood plasma.
When used in therapeutic concentrations, approximately 95% of paroxetine is bound to plasma proteins.
In elderly patients and patients with renal or hepatic insufficiency, an increase in the concentration of paroxetine in the blood plasma is observed, but it does not exceed the concentration fluctuations in healthy adults.
Indication
Depression. Treatment of depression of any type, including reactive and severe depression, including depression accompanied by anxiety. In case of satisfactory response to treatment, continued therapy is effective in preventing relapses of depression.
Obsessive-compulsive disorder. Treatment and prevention of relapses of obsessive-compulsive disorder.
Panic disorder. Treatment 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 and prevention of relapses of generalized anxiety disorder.
Post-traumatic stress disorder. Treatment of post-traumatic stress disorder.
Contraindication
Paroxin 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 Paroxin.
Paroxetine should not be used concomitantly with thioridazine and 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.
Concomitant use of paroxetine with serotonergic drugs may lead to a 5-HT-associated effect (serotonin syndrome).
During the period of simultaneous use of paroxetine with lithium, fentanyl, tramadol or St. John's wort, caution should be exercised with mandatory careful monitoring of the patient's clinical condition to avoid the development of serotonin syndrome. For this reason, Paroxetine should not be prescribed simultaneously with drugs containing tryptophan, triptans, as well as other selective serotonin reuptake inhibitors.
The concomitant use of paroxetine and MAO inhibitors (including linezolid, an antibiotic that is a reversible non-selective MAO inhibitor), and methylthioninium chloride (methylene blue) is contraindicated (see section "Contraindications").
Pimozide.
Concomitant administration of a single low dose of pimozide (2 mg) and paroxetine has been associated with increased pimozide levels. This is due to the known CYP2D6 inhibitory properties of paroxetine. Due to the narrow therapeutic index of pimozide and its potential to prolong the QT interval, concomitant administration of pimozide and paroxetine is contraindicated.
Drugs that affect the metabolism of liver enzymes.
The metabolism and pharmacokinetic parameters of paroxetine may be altered by concomitant use of drugs that induce or inhibit the metabolism of liver enzymes.
When paroxetine is used concomitantly with drugs that inhibit enzymes, it is recommended to prescribe the lowest effective dose. When used concomitantly with drugs that induce enzymes (carbamazepine, rifampicin, phenobarbital, phenytoin), there is no need to change the initial dose of paroxetine. The dose should be changed during further treatment according to the clinical effect (tolerability and efficacy).
Since paroxetine is highly bound to plasma proteins, concomitant use with other drugs that are highly bound to plasma proteins may result in an increase in the free fraction of one of the drugs.
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 administration 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.
CYP2D6.
Paroxetine inhibits the activity of cytochrome P450 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, which may cause QT prolongation with associated severe ventricular arrhythmias (e.g., torsades de pointes) and sudden death; therefore, thioridazine and paroxetine should not be used concomitantly), risperidone, atomoxetine, some antiarrhythmics (e.g., propafenone and flecainide), and metoprolol.
Paroxetine may reduce the effectiveness of tamoxifen (see section "Special warnings and precautions for use").
Concomitant use of paroxetine and terfenadine, alprazolam, and other drugs that are substrates for CYP3A4 is not dangerous.
Paroxetine can be prescribed concomitantly with haloperidol, amylobarbitone, and oxazepam.
The absorption or pharmacokinetics of paroxetine have been shown to be unaffected or substantially unaffected (i.e., do not require dosage adjustment) by the following factors: food, antacids, digoxin, propranolol, alcohol. However, concomitant administration of paroxetine and digoxin should be undertaken with caution due to a decrease in digoxin AUC.
Paroxetine does not increase the impairment of mental and motor reactions caused by alcohol, however, drinking alcoholic beverages during treatment with Paroxetine is not recommended.
Anticoagulants.
Paroxin should be administered with caution simultaneously with warfarin and other anticoagulants, as their interaction may lead to enhanced anticoagulant activity and increase the risk of bleeding.
When NSAIDs/acetylsalicylic acid are used concomitantly with paroxetine, a pharmacodynamic interaction may occur, which may lead to an increased risk of bleeding. Paroxetine should be administered with caution in conjunction with drugs that affect platelet function or increase the risk of bleeding.
Application features
Deterioration of clinical condition and risk of suicide.
Young adult patients, especially 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 depressive symptoms and/or suicidal ideation and behavior, whether or not they are taking antidepressants. This risk persists until significant remission occurs. The risk of suicide may increase in the early stages of recovery.
Other psychiatric disorders for which Paroxetine is prescribed may be associated with an increased risk of suicidal behaviour, and such disorders may also be combined with major depressive disorders. Patients with a history of suicidal behaviour and intentions, young patients and patients with persistent suicidal thoughts before the start of treatment are a group of patients at increased risk of suicide attempts and suicidal thoughts. All patients should be closely monitored for any worsening of the patient's condition (including the development of new symptoms) and suicidal behaviour during treatment, particularly at the beginning of treatment or during changes in dose (both increase and decrease). Patients (and their caregivers) 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 intentions/behaviour or thoughts of harming themselves and to seek medical advice immediately if they present.
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 deterioration (including the development of new symptoms) and/or the appearance of suicidal thoughts/behavior, especially if these symptoms are severe, develop suddenly, or have not been previously observed in the patient, it is necessary to change the drug regimen up to and including its withdrawal.
Akathisia.
The use of paroxetine or other selective serotonin reuptake inhibitors may be associated with the development of akathisia, a condition characterised by a feeling of inner restlessness and psychomotor agitation, such as an inability to sit or stand, combined with a subjective feeling of discomfort. This is most likely to occur during the first weeks of treatment.
Serotonin syndrome/neuroleptic malignant syndrome.
In isolated cases, treatment with paroxetine may be associated with the development of serotonin 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 of 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 developing serotonin syndrome.
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 examined to identify any risk of developing bipolar disorder. Such examination should include a detailed study of the patient's medical history, including the presence of suicidal attempts, bipolar disorders and depression in family members. It should be noted that Paroxin is not used to treat depression in bipolar disorder. Paroxin 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. 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.
Studies investigating the risk of bone fractures with some antidepressants, including selective serotonin reuptake inhibitors, have reported an association with fractures. The risk appears to be treatment-emergent and is highest in the early stages of therapy. The possibility of bone fractures should be considered when treating with paroxetine.
Monoamine oxidase inhibitors.
Treatment with Paroxin should be initiated with caution, no earlier than 2 weeks after discontinuation of MAO inhibitors.
Renal/hepatic failure.
Caution should be exercised when prescribing the drug to patients with severe renal (creatinine clearance less than 30 ml/min) or hepatic insufficiency, as plasma concentrations of paroxetine are increased in such patients. In this regard, the dose of Paroxetine should be reduced to the minimum effective dose.
Diabetes.
In patients with diabetes mellitus, treatment with serotonin reuptake inhibitors may alter the glycemic profile, so the dose of insulin and/or oral hypoglycemic drugs should be adjusted.
Epilepsy.
Paroxetine, like other antidepressants, should be used with caution in the treatment of patients with epilepsy. If the patient develops seizures, Paroxetine should be discontinued.
Electroconvulsive therapy.
There is only limited clinical experience with the use of paroxetine in combination with electroconvulsive therapy.
Glaucoma.
Paroxetine, like other serotonin reuptake inhibitors, can cause mydriasis and should be used with caution in 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 bleeding) has been reported following treatment with paroxetine. Therefore, Paroxetine should be used with caution in patients receiving concomitant medications with an increased risk of bleeding, or in patients with a history of or predisposition to frequent bleeding.
Heart disease.
When treating patients with concomitant cardiac disease, the usual precautions should be observed.
Symptoms observed during paroxetine withdrawal.
Fertility.
Some clinical studies have shown that selective serotonin reuptake inhibitors, including paroxetine, may have an effect on sperm quality. These effects are thought to reverse after discontinuation of treatment. Altered sperm quality may affect the fertility of some men.
Use during pregnancy or breastfeeding
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.
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 selective serotonin reuptake inhibitors during this period, although a causal relationship with the drug has not been established. The following effects have been reported: respiratory distress, cyanosis, apnea, seizures, 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 selective serotonin reuptake inhibitors (including paroxetine) in pregnant women, especially in late pregnancy, is associated with an increased risk of persistent pulmonary hypertension in the newborn. In women who used SSRIs in late pregnancy, this risk was increased 4-5 times compared with the general group of patients.
Breast-feeding.
Small amounts of paroxetine are excreted in breast milk. No evidence of effects on the newborn has been found, however Paroxetine should not be used during breast-feeding unless the expected benefit to the mother outweighs the potential risk to the child.
Ability to influence reaction speed when driving vehicles or other mechanisms
Clinical experience with paroxetine suggests that it does not affect cognitive function or psychomotor reactions. However, as with other psychoactive drugs, patients should be warned about the possible impairment of their ability to drive or operate machinery during treatment.
Method of administration and doses
General recommendations.
Paroxin is administered orally, it is recommended to take it once a day, in the morning, during a meal. The tablet should be swallowed without chewing.
As with all other antidepressants, the dose should be carefully titrated individually during the first 2-3 weeks of treatment and then adjusted according to clinical response.
The course of treatment should be long enough to ensure resolution of symptoms. As with other medications for the treatment of psychiatric disorders, abrupt withdrawal of the drug should be avoided.
Depression. The recommended dose is 20 mg per day. If this dose is ineffective, the dose is increased by 10 mg per day to a maximum dose of 50 mg per day to improve the condition. The dose can be adjusted 2-3 weeks after the start of therapy. For the treatment of acute episodes of depression, the duration of treatment should be several months or more.
Obsessive-compulsive disorder. The recommended dose is 40 mg per day. Treatment should be initiated with a dose of 20 mg and gradually increased by 10 mg weekly. If necessary, the dose may be increased to a maximum dose of 60 mg.
Panic disorder. The recommended dose is 40 mg per day. Therapy should be initiated at a dose of 10 mg per day, increasing by 10 mg weekly. To achieve the appropriate therapeutic effect, the dose of Paroxin can be increased to a maximum dose of 50 mg per day.
Social anxiety disorder/social phobia. The recommended dose is 20 mg per day. For some patients, the dose may be increased gradually by 10 mg per day, depending on the clinical effect of treatment, up to 50 mg per day. The interval between dose increases should be at least 1 week.
Generalized anxiety disorder. The recommended dose is 20 mg per day. For some patients with insufficient efficacy at 20 mg, the dose may be gradually increased by 10 mg per day, depending on the clinical effect, up to 50 mg per day.
Post-traumatic stress disorder. The recommended dose is 20 mg per day. For some patients with insufficient efficacy at 20 mg, the dose may be gradually increased by 10 mg per day, depending on the clinical effect, up to 50 mg per day.
Elderly patients: Treatment is initiated with the usual starting dose for adults, which can then be gradually increased to 40 mg per day.
Paroxin withdrawal.
As with other drugs for the treatment of mental illness, abrupt withdrawal of the drug should be avoided. A gradual tapering regimen may be used, involving a reduction in the daily dose by 10 mg per day at weekly intervals. After reaching a dosage regimen of 20 mg per day, patients should continue taking the drug at this dose for another week before completely discontinuing it. If 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.
Children.
Paroxetine is not indicated for the treatment of children. Controlled clinical trials have not demonstrated efficacy and there is no supportive data for the use of paroxetine in the treatment of depression in children.
Overdose
Paroxetine therapy is safe over a wide range of doses. Signs of overdose include nausea, vomiting, fever, changes in blood pressure, involuntary muscle contractions, anxiety, and tachycardia.
All these effects in patients in most cases pass without serious consequences even after taking a dose of 2000 mg. Sometimes coma or changes in ECG parameters were observed, very rarely fatal outcomes were noted, but mainly in such cases paroxetine was used together with other psychotropic drugs or with alcohol.
Specific antidote is unknown.
Treatment. It is necessary to remove the drug from the stomach by inducing vomiting or performing gastric lavage. Supportive therapy is indicated with monitoring of vital signs and careful observation of the patient's condition in a hospital setting.
Adverse reactions
From the blood system: increased bleeding of the skin and mucous membranes (ecchymoses), thrombocytopenia.
Immune system disorders: allergic reactions (including urticaria and angioedema).
On the part of the endocrine system: possible syndrome due to insufficient secretion of antidiuretic hormone.
Metabolism and digestive disorders: increased cholesterol levels, decreased appetite, hyponatremia. Hyponatremia is observed mainly in elderly patients and is sometimes associated with the syndrome of inappropriate antidiuretic hormone secretion.
Nervous system and psyche: drowsiness, insomnia, agitation, abnormal dreams (including nightmares), confusion, hallucinations, manic reactions, restlessness, depersonalization, panic attacks, suicidal ideation and suicidal behavior.
Dizziness, tremor, headache, extrapyramidal disorders, convulsions, akathisia, restless legs syndrome, 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 patients treated with neuroleptics.
From the organs of vision: decreased visual acuity, mydriasis, acute glaucoma.
On the part of the organs of hearing: ringing in the ears.
Cardiovascular system: sinus tachycardia, postural hypotension, transient increase or decrease in blood pressure, bradycardia.
Respiratory system: yawning.
Skin and subcutaneous tissue disorders: increased sweating, itching, skin rashes, photosensitivity reactions, severe skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis).
Renal and urinary disorders: urinary retention, urinary incontinence.
Reproductive system: sexual dysfunction, hyperprolactinemia/galactorrhea, priapism.
Musculoskeletal system: arthralgia, myalgia.
General disorders: asthenia, weight gain, peripheral edema.
Symptoms caused by drug withdrawal.
As with other drugs for the treatment of psychiatric disorders, withdrawal of Paroxin (especially sudden) may lead to symptoms such as dizziness, sensory disturbances (including paraesthesia, electric shock sensations, tinnitus), sleep disturbances (including vivid dreams), agitation or anxiety, nausea, headache, tremor, confusion, diarrhea and sweating, palpitations, agitation, emotional lability, visual disturbances. In most patients, these symptoms are mild to moderate in severity and resolve without treatment. Symptoms usually occur within the first few days after discontinuation of the drug, and isolated cases of such symptoms have been reported in patients who have inadvertently missed taking the drug. These symptoms usually resolve spontaneously within 2 weeks, although in some patients this process may be longer (2-3 months or longer). There is no particular risk group for these symptoms, so if Paroxin needs to be discontinued, the dose should be reduced gradually over several weeks or months, depending on the individual characteristics of the patient.
Expiration date
3 years.
Storage conditions
Store out of the reach of children, in the original packaging at a temperature not exceeding 25 ºС.
Packaging
10 tablets in a blister; 3 or 6 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
Pharma Start LLC, Ukraine.
Location of the manufacturer and its business address
Ukraine, 03124, Kyiv, I. Lepse Blvd., 8.
