Paroxetine - instructions for use, dose, side effects, contraindications

Each tablet, film-coated, as an active substance contains - 22.76 mg of paroxetine hydrochloride hemihydrate (in terms of paroxetine base - 20.00 mg);

Excipients: calcium hydrophosphate - 110.00 mg, cellulose microcrystalline - 60.18 mg, copovidone - 6.60 mg, crospovidone - 5.50 mg, magnesium stearate - 2.86 mg, silicon colloidal dioxide - 1.10 mg, talc - 11.00 mg; composition of the membrane: hypromellose - 5.56 mg, talc - 2.22 mg, titanium dioxide - 1.33 mg, macrogol-6000 - 0.89 mg.

Description:Round biconvex tablets covered with a film shell, white, with a rough surface, with a risk on one side.

Pharmacotherapeutic group:antidepressant.

ATX: & nbsp

N.06.A.B Selective serotonin reuptake inhibitors

N.06.A.B.05 Paroxetine

Pharmacodynamics:

Paroxetine is a potent and selective 5-hydroxytryptamine reuptake inhibitor (5-HT, serotonin). It is believed that its antidepressant activity and effectiveness in the treatment of obsessive-compulsive (OCD) and panic disorder is due to the specific inhibition of reuptake of serotonin in neurons of the brain. By its chemical structure paroxetine differs from tricyclic, tetracyclic and other known antidepressants.

Paroxetine has a weak affinity for muscarinic cholinergic receptors, and studies in animals have shown that it has only weak anticholinergic properties.

In accordance with the selective effect of paroxetine, studies in vitro showed that, unlike tricyclic antidepressants, it has a weak affinity for a-1, a-2 and P-adrenoreceptors, as well as for dopamine (D2), 5-HT1-like, 5NT2 and histamine (H1) receptors.This lack of interaction with postsynaptic receptors in vitro is confirmed by the results of studies in vivo, which demonstrated the lack of paroxetine ability to oppress the central nervous system (CNS) and cause arterial hypotension.

Pharmacodynamic effects

Paroxetine does not impair psychomotor functions and does not enhance the inhibitory effect of ethanol on the central nervous system.

Like other selective serotonin reuptake inhibitors, paroxetine causes symptoms of excessive stimulation of 5-HT-receptors when administered to animals that previously received monoamine oxidase (MAO) inhibitors or tryptophan.

Studies of EEG behavior and changes demonstrated that paroxetine causes mild activating effects at doses in excess of those required to inhibit serotonin reuptake. By its very nature, its activating properties are not "amphetamine-like".

Studies in animals have shown that paroxetine does not affect the cardiovascular system.

In healthy individuals paroxetine does not cause clinically significant changes in blood pressure, heart rate and ECG.

Studies have shown that, unlike antidepressants, which oppress norepinephrine reuptake, paroxetine has much less ability to inhibit the anti-hypertensive effects of guanethidine.

Pharmacokinetics:

Absorption. After oral administration paroxetine is well absorbed and subjected to the metabolism of the first passage.

Due to the metabolism of the first passage, less paroxetine is supplied to the systemic bloodstream than that absorbed from the gastrointestinal tract. As the amount of paroxetine increases in the body with a single intake of large doses or with repeated intake of usual doses, the partial metabolism of the first passage occurs and the clearance of paroxetine from the plasma decreases. This leads to a disproportionate increase in the concentrations of paroxetine in the plasma. Therefore, its pharmacokinetic parameters are not stable, resulting in nonlinear kinetics. It should be noted, however, that the nonlinearity is usually poorly expressed and is observed only in those patients who, when taking low doses of the drug in the plasma, achieve low levels of paroxetine.

Stable concentrations in the plasma are reached 7-14 days after the start of paroxetine treatment, its pharmacokinetic parameters most likely do not change during prolonged therapy.

Distribution. Paroxetine widely distributed in tissues, and pharmacokinetic calculations show that only 1% of the total amount of paroxetine present in the body remains in the plasma. At therapeutic concentrations, approximately 95% of paroxetine in the plasma is associated with proteins.

There was no correlation between paroxetine concentrations in plasma and its clinical effect (ie, with adverse reactions and efficacy).

Determined that paroxetine in small quantities penetrates into the breast milk of women, as well as in embryos and fruits of laboratory animals

Metabolism. The main metabolites of paroxetine are polar and conjugated oxidation and methylation products, which are easily eliminated from the body. Given the relative lack of pharmacological activity in these metabolites, it can be argued that they do not affect the therapeutic effects of paroxetine.

Metabolism does not impair the ability of paroxetine to selectively inhibit the reuptake of serotonin.

Elimination. Kidney in the form of unchanged paroxetine excreted less than 2 % of the dose taken, whereas the excretion of metabolites reaches 64% of the dose. About 36% of the dose is excreted through the intestine, probably getting into it with bile; Excretion through the intestine of unchanged paroxetine is less than 1% of the dose. In this way, paroxetine is eliminated almost entirely by metabolism.

Excretion of metabolites is biphasic: first it is the result of metabolism of the first passage, then it is controlled by systemic elimination of paroxetine.

The half-life of paroxetine varies, but usually is about 1 day (16-24 hours).

Indications:

Depression

Depression of all types, including reactive and severe depression, as well as depression, accompanied by anxiety.

In the treatment of depressive disorders paroxetine has approximately the same efficacy as tricyclic antidepressants. There is evidence that paroxetine can give good results in patients in whom standard antidepressant therapy has proven ineffective.

Taking paroxetine in the morning does not adversely affect the quality and duration of sleep. In addition, as the effect of paroxetine treatment appears, sleep can improve. When using short-acting hypnotic drugs in combination with antidepressants, no additional side effects occurred. In the first few weeks of therapy paroxetine effectively reduces the symptoms of depression and suicidal thoughts.

The results of studies in which patients took paroxetine for up to 1 year, showed that the drug effectively prevents relapses of depression.

- Obsessive-compulsive disorder

Paroxetine is effective in treating obsessive-compulsive disorder (ROC), including as a means of supporting and prophylactic therapy.

Besides, paroxetine effectively prevented the recurrence of OCD.

- Panic disorder

Paroxetine is effective in the treatment of panic disorder with and without agoraphobia, including as a means of supporting and preventive therapy.

It was found that in the treatment of panic disorder a combination of paroxetine and cognitive-behavioraltherapy is significantly more effective than the isolated use of cognitive-behavioral therapy.

Besides, paroxetine effectively prevented the recurrence of panic disorder.

- Social phobia

Paroxetine is an effective treatment for social phobia, including as a long-term supportive and preventive therapy.

- Generalized anxiety disorder

Paroxetine is effective in generalized anxiety disorder, including as a long-term maintenance and prophylactic therapy. Paroxetine also effectively prevents relapses in this disorder.

- Post-Traumatic Stress Disorder

Paroxetine is effective in the treatment of post-traumatic stress disorder

Contraindications:

- Hypersensitivity to paroxetine and its components.

- Combined use of paroxetine with monoamine oxidase inhibitors (MAO). Paroxetine should not be used concurrently with MAO inhibitors or within 2 weeks after their withdrawal. MAO inhibitors can not be administered within 2 weeks after treatment with paroxetine.

- Combined use with thioridazine. Paroxetine should not be prescribed in combination with thioridazine, because, like other drugs that inhibit the activity of the liver enzyme CYP450 2D6, paroxetine may increase the concentration of thioridazine in the plasma, which may lead to lengthening of the interval QT and associated with this arrhythmia "pirouette" (torsades de pointes) and sudden death.

- Combined use with pimozide.

- Use in children and adolescents younger than 18 years.

Carefully:

Pregnancy and lactation:

Fertility

Selective serotonin reuptake inhibitors (SSRIs) (including paroxetine) can affect the quality of seminal fluid. This effect is reversible after discontinuation of the drug. Change in semen properties can lead to impaired fertility.

Pregnancy

Studies in animals have not revealed teratogenic or selective embryotoxic activity in paroxetine.

Recent epidemiological studies of pregnancy outcomes with antidepressant medications in the first trimester have shown an increased risk of congenital anomalies, in particular the cardiovascular system (eg, interventricular and atrial septal defects) associated with paroxetine.According to the data, the occurrence of cardiovascular system defects with paroxetine during pregnancy is approximately 1/50, whereas the expected occurrence of such defects in the general population is approximately 1/100 of the newborns. When paroxetine is prescribed, it is necessary to consider the possibility of alternative treatment in pregnant women and pregnant women planning pregnancy. There are reports of premature birth in women who received during pregnancy paroxetine or other preparations of the SSRI group, but the causal relationship between these drugs and preterm labor is not established. Paroxetine Do not use during pregnancy, if its potential benefit does not exceed the possible risk.

It is necessary to closely monitor the health of those newborns whose mothers have been taking paroxetine in late pregnancy, because there are reports of complications in newborns exposed to paroxetine or other SSRI drugs in the third trimester of pregnancy. It should be noted, however, that in this case the cause-and-effect relationship between these complications and this drug therapy has not been established.The clinical complications described included: respiratory distress syndrome, cyanosis, apnea, convulsive seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, tremor, nervous irritability, irritability, lethargy, constant crying and drowsiness . In some reports, the symptoms have been described as neonatal manifestations of withdrawal syndrome. In most cases, the described complications occurred immediately after birth or shortly after birth (<24 h).

According to epidemiological studies, the intake of SSRIs (including paroxetine) in late pregnancy is associated with an increased risk of developing persistent pulmonary hypertension in newborns. Increased risk is observed in children born to mothers who took SSRIs in late pregnancy, 4-5 times higher than observed in the general population (1-2 per 1000 pregnancies). Lactation

Insignificant amounts of paroxetine penetrate into breast milk. Nevertheless, paroxetine should not be taken during breastfeeding, except when its benefit to the mother exceeds the potential risks to the child.

Dosing and Administration:

Paroxetine is recommended to be taken 1 time a day in the morning during a meal. The tablet should be swallowed whole, without chewing.

- Depression

The recommended dose for adults is 20 mg per day. If necessary, depending on the therapeutic effect, the daily dose may increase weekly by 10 mg per day to a maximum dose of 50 mg per day. As with any antidepressant medication, should evaluate the effectiveness of therapy and, if necessary, adjust the dose of paroxetine 2-3 weeks after the start of treatment and in the future, depending on the clinical indications.

To relieve depressive symptoms and prevent relapses, adequate duration of stopping and maintenance therapy should be observed. This period can be several months.

- Obsessive-compulsive disorder

The recommended dose is 40 mg per day. Treatment begins with a dose of 20 mg per day, which can be increased weekly by 10 mg per day. If necessary, the dose can be increased to 60 mg per day. It is necessary to observe adequate duration of therapy (several months and longer).

- Panic disorder

The recommended dose is 40 mg per day. Treatment of patients should begin with a dose of 10 mg per day and weekly increase the dose by 10 mg per day, focusing on the clinical effect. If necessary, the dose may be increased to 60 mg per day.

A low initial dose is recommended to minimize the possible increase in symptoms of panic disorder, which can occur at the beginning of treatment with any antidepressant.

It is necessary to observe adequate periods of therapy (several months and longer).

- Social phobia

The recommended dose is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day, depending on the clinical effect to 50 mg per day.

- Generalized anxiety disorder

The recommended dose is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day, depending on the clinical effect to 50 mg per day.

- Post-traumatic stress disorder disorder

The recommended dose is 20 mg per day. If necessary, the dose may be increased weekly by 10 mg per day, depending on the clinical effect to 50 mg per day.

general information

Paroxetine withdrawal

As in the treatment of other psychotropic drugs, avoid abrupt withdrawal of paroxetine.

The following cancellation schedule can be recommended: reduction of the daily dose by 10 mg per week; after reaching a dose of 20 mg per day, patients continue to take this dose for 1 week, and only after that the drug is canceled completely.

If withdrawal symptoms develop during dose reduction or after drug withdrawal, it is advisable to resume taking the previously prescribed dose. In the future, the doctor may continue to reduce the dose, but more slowly.

Individual patient groups

Elderly patients

In elderly patients, paroxetine concentrations in plasma can be increased, but the range of its plasma concentrations coincides with those in younger patients. In this category of patients, therapy should be started with a dose recommended for adults, which can be increased to 40 mg per day.

Patients with impaired renal or hepatic function

Paroxetine concentrations in plasma are elevated in patients with severe renal impairment (creatinine clearance less than 30 mL / min) and in patients with impaired liver function.Such patients should be given doses of the drug that are in the lower part of the therapeutic dose range.

Children and teenagers (under the age of 18)

The use of paroxetine in this category of patients is contraindicated.

Side effects:

The frequency and intensity of some of the following side effects of paroxetine may decrease as the treatment continues, and such effects usually do not require withdrawal of the drug. Side effects are stratified below by organ systems and frequency. The frequency gradient is the following: very frequent (> 1/10), frequent (> 1/100, <1/10), infrequent (> 1/1000, <1/100), rare (> 1/10 000, <1 / 1000) and very rare (<1/10 000), including individual cases.

Violations of the blood and lymphatic system

Infrequent: abnormal bleeding, mainly hemorrhage into the skin and mucous membranes (most often - bruising).

Very rare: thrombocytopenia.

Immune system disorders

Very rare: allergic reactions (including hives and angioedema).

Endocrine disorders

Very rare: syndrome of impaired secretion of antidiuretic hormone.

Metabolic disorders and eating disorders Frequent: decreased appetite, increased cholesterol.

Rare: hyponatremia.

Mental disorders

Frequent: drowsiness, insomnia, agitation, unusual dreams (including nightmares).

Infrequent: confusion, hallucinations.

Rare: manic reactions.

These symptoms can also be caused by the disease itself.

Disturbances from the nervous system Frequent: dizziness, tremor, headache.

Infrequent: extrapyramidal disorders.

Rare: cramps, akathisia, restless legs syndrome.

Very rare: serotonin syndrome (symptoms may include agitation, confusion, increased sweating, hallucinations, hyperreflexia, myoclonus, tachycardia with tremors and tremors).

Vision disorders

Frequent: blurred vision.

Infrequent: mydriasis.

Very rare: acute glaucoma.

Heart Disease Infrequent: sinus tachycardia.

Vascular disorders Infrequent: postural hypotension.

Disturbances from the respiratory, thoracic and mediastinal organs

Frequent: yawn.

Gastrointestinal disorders

Very Frequent: nausea.

Frequent: constipation, diarrhea, vomiting, dry mouth.

Very rare: gastrointestinal bleeding.

Hepatobiliary disorders

Rare: increased levels of hepatic enzymes.

Very rare: hepatitis, sometimes accompanied by jaundice, and / or hepatic failure. Sometimes there is an increase in levels of hepatic enzymes.

Disturbances from the skin and subcutaneous tissues

Frequent: sweating.

Infrequent: skin rashes.

Very rare: photosensitivity reactions, severe skin reactions (including polymorphic erythema, Stephen-Johnson syndrome and toxic epidermal necrolysis).

Violations from the kidneys and urinary tract

Rare: urinary retention, urinary incontinence.

Disorders from the reproductive system and mammary glands

Very Frequent: sexual dysfunction.

Rare: hyperprolactinemia / galactorrhea.

Other

Frequent: asthenia, weight gain.

Very rare: peripheral edema.

Symptoms that occur when discontinuing paroxetine treatment:

Frequent: dizziness, sensory disturbances, sleep disorders, anxiety, headache. Infrequent: agitation, nausea, tremor, confusion, sweating, diarrhea:

As with the abolition of many psychotropic drugs, discontinuation of treatment with paroxetine (particularly sharp) can cause symptoms such as dizziness, sensory disturbances (including paresthesia, sensation of electric current discharge and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, headache, tremors, confusion, diarrhea and sweating. In most patients, these symptoms are mild or moderate and go away spontaneously. No group of patients is known to be at increased risk for such symptoms; so if in the treatment of paroxetine is no longer necessary, its dose should be reduced slowly until the drug is completely discontinued.

Overdose:

With an overdose of paroxetine in addition to the symptoms described in the section "Side effects" are observed fever, blood pressure changes, involuntary muscle contractions, anxiety and tachycardia.

The condition of patients usually normalized without serious consequences, even with a single dose of up to 2000 mg. A number of reports described symptoms such as coma, and ECG changes, deaths were very rare, usually in situations where patients received paroxetine together with other psychotropic drugs or with alcohol.

Treatment

There is no specific antidote of paroxetine. Treatment should consist of general measures used for an overdose of any antidepressant. Supportive therapy and frequent monitoring of basic physiological parameters are shown. The patient should be treated in accordance with the clinical picture or in accordance with the recommendations of the National Toxicology Center.

Interaction:

Serotonergic drugs:

The use of paroxetine, as well as other drugs of the SSRI group, simultaneously with serotonergic drugs (including L-tryptophan, triptans, tramadol, preparations of the SSRIs group, fentanyl, lithium and herbal remedies containing St. John's wort pitted) can cause effects associated with 5-HT (serotonin syndrome). The use of paroxetine with MAO inhibitors (including linezolid, an antibiotic that transforms into a non-selective MAO inhibitor) is contraindicated.

Pimozide:

In a study of the possibility of sharing paroxetine and pimozide at a low dose (2 mg once), an increase in the level of pimozide was recorded.This fact is due to the known property of paroxetine to inhibit the system CYP2D6. Due to the narrow therapeutic index of pimozide and its known ability to lengthen the interval QT, the combined use of pimozide and paroxetine is contraindicated.

When using these drugs in combination with paroxetine, care must be taken and careful clinical monitoring performed.

Enzymes involved in the metabolism of drugs:

Metabolism and pharmacokinetics of paroxetine can change under the influence of induction or inhibition of enzymes that participate in the metabolism of drugs. When paroxetine is used simultaneously with an inhibitor of enzymes involved in the metabolism of drugs, one should evaluate the feasibility of using a dose of paroxetine at the bottom of the therapeutic dose range. The initial dose of paroxetine should not be adjusted if it is used concomitantly with a drug that is a known inducer of enzymes involved in the metabolism of drugs (for example, carbamazepine, rifampicin, phenobarbital, phenytoin).Any subsequent adjustment of the dose of paroxetine should be determined by its clinical effects (tolerability and efficacy).

Fosamprenavir / ritonavir:

The combined use of fosamprenavir / ritonavir with paroxetine resulted in a significant decrease in paroxetine concentration in the blood plasma.

Any subsequent adjustment of the dose of paroxetine should be determined by its clinical effects (tolerability and efficacy).

Procyclidine:

Daily intake of paroxetine significantly increases the concentration of procyclidine in blood plasma. When anticholinergic effects occur, the dose of procyclidine should be reduced.

Anticonvulsants: carbamazepine, phenytoin, sodium valproate.

Simultaneous use of paroxetine and these drugs does not affect their pharmacokinetics and pharmacodynamics in patients with epilepsy.

The ability of paroxetine to inhibit enzyme CYP2D6

Like other antidepressants, including other SSRIs, paroxetine inhibits the hepatic enzyme CYP2D6, related to the cytochrome P450 system. Inhibition of enzyme CYP2D6 can lead to an increase in plasma concentrations of simultaneously used drugs that are metabolized by this enzyme.These drugs include tricyclic antidepressants (for example, amitriptyline, nortriptyline, imipramine and desipramine), neuroleptics of the phenothiazine series (perphenazine and thioridazine), risperidone, atomoxetine, some antiarrhythmic agents of type 1c (for example, propafenone and flecainide) and metoprolol. The use of paroxetine, which inhibits the system CYP2D6, can lead to a decrease in the concentration of active metabolite tamoxifen in blood plasma, and as a consequence, reduce the effectiveness of tamoxifen.

CYP3A4

Investigation of interaction in vivo with simultaneous application, under conditions of equilibrium, of paroxetine and terfenadine, which is the substrate of the enzyme CYP3A4, showed that paroxetine does not affect the pharmacokinetics of terfenadine. In a similar interaction study in vivo There was no effect of paroxetine on pharmacokinetics of alprazolam, and vice versa. Simultaneous use of paroxetine with terfenadine, alprazolam and other drugs that serve as the substrate of the enzyme CYP3A4, can hardly cause harm to the patient.

Clinical studies have shown that the absorption and pharmacokinetics of paroxetine is independent or practically independent (i.e.the existing dependence does not require a dose change) from:

- food

- antacids

- digoxin

- propranolol

- alcohol: paroxetine does not increase the negative effect of alcohol on psychomotor functions, however, it is not recommended to simultaneously take paroxetine and alcohol.

Special instructions:

Clinical deterioration and suicidal risk of adults

Young patients, especially those suffering from major depressive disorder, may be at increased risk of suicidal behavior during paroxetine therapy. An analysis of placebo-controlled studies in adults with mental illnesses indicates an increase in the incidence of suicidal behavior in young patients (aged 18-24 years) when taking paroxetine compared to the placebo group (2.19% to 0.92%, respectively ), although this difference is not considered statistically significant. In patients of older age groups (from 25 to 64 years and older than 65 years), an increase in the incidence of suicidal behavior was observed. In adults of all age groups suffering from major depressive disorder, there was a statistically significant increase in casessuicidal behavior against the background of paroxetine treatment compared with the placebo group (the occurrence of suicidal attempts: 0.32% to 0.05%, respectively). However, most of these cases, when taking paroxetine (8 of 11), were registered in young patients aged 18-30 years. Data obtained in the study in patients with major depressive disorder may indicate an increase in the incidence of cases suicidal behavior in patients younger than 24 years old, suffering from various mental disorders. In patients with depression, the exacerbation of symptoms of this disorder and / or the appearance of suicidal thoughts and suicidal behavior (suicidal) can be observed regardless of whether they receive antidepressants. This risk persists until a pronounced remission is achieved. Improvement of the patient's condition may be absent in the first weeks of treatment or more, and therefore the patient should be closely monitored for the timely detection of clinical exacerbation and suicidality, especially at the beginning of the course of treatment, as well as during periods of dose changes, whether they increase or decrease.Clinical experience with the use of all antidepressants shows that the risk of suicide may increase in the early stages of recovery.

Other mental disorders for which treatment is used paroxetine, too, may be associated with an increased risk of suicidal behavior. In addition, these disorders can be comorbid conditions associated with a major depressive disorder. Therefore, in treating patients suffering from other mental disorders, the same precautions should be followed as in the treatment of major depressive disorder.

The greatest risk of suicidal thoughts or suicidal attempts is experienced by patients with a history of suicidal behavior or suicidal ideation, young patients, and patients with severe suicidal thoughts prior to treatment, and therefore all need to be given special attention during treatment. Patients (and those who care for them) need to be warned about the need to monitor their deterioration and / or the appearance of suicidal thoughts / suicidal behavior or thoughts of self-harm during the course of treatment, especially at the beginning of treatment, during a dose change (increase and decrease).If these symptoms occur, seek medical help immediately.

It should be remembered that such symptoms as agitation, akathisia or mania may be associated with a major disease or be a consequence of the therapy used. If symptoms of clinical deterioration (including new symptoms) and / or suicidal thoughts / behavior occur, especially if they suddenly appear, the severity of the manifestations increases, or if they are not part of the previous symptom-complex in this patient, withdrawal of the drug.

Akathisia

Occasionally, treatment with paroxetine or another drug of the group of selective serotonin reuptake inhibitors is accompanied by the appearance of akathisia, which is manifested by a feeling of internal anxiety and psychomotor agitation, when the patient can not sit or stand still; At akathisia the patient usually experiences subjective discomfort. The likelihood of akathisia is highest in the first few weeks of treatment.

Serotonin syndrome / malignant neuroleptic syndrome In rare cases, against the background of paroxetine treatment, serotonin syndrome or symptomatic similar to a malignant neuroleptic syndrome may occur, especially if paroxetine are used in combination with other serotonergic drugs and / or antipsychotics. These syndromes present a potential threat to life, and therefore treatment with paroxetine should be discontinued if they occur (they are characterized by groups of symptoms such as hyperthermia, muscle rigidity, myoclonus, autonomic disorders with possible rapid changes in vital signs, changes in mental status, including confusion, irritability, extremely severe agitation, progressing to delirium and coma), and begin supporting symptomatic therapy. Paroxetine should not be given in combination with serotonin precursors (such as L-tryptophan, oxytryptan) in connection with the risk of developing serotonergic syndrome.

Mania and bipolar disorder

A major depressive episode may be the initial manifestation of bipolar disorder.It is generally accepted (although not proven by controlled clinical trials) that treating such an episode with an antidepressant alone may increase the likelihood of an accelerated development of a mixed / manic episode in patients at risk of bipolar disorder. Before starting treatment with an antidepressant, a thorough screening should be performed to assess the risk of a bipolar disorder in the patient; such screening should include the collection of a detailed psychiatric history, including data on the presence in the family of cases of suicide, bipolar disorder and depression. Paroxetine It is not registered for the treatment of a depressive episode in the context of bipolar disorder. Paroxetine should be used with caution in patients who have a history of mania.

Inhibitors of monoamine oxidase (MAO)

Treatment with paroxetine should be started cautiously no earlier than 2 weeks after discontinuation of therapy with MAO inhibitors; The dose of paroxetine should be increased gradually until an optimal therapeutic effect is achieved.

Impaired kidney or liver function

It is advisable to use caution when treating paroxetine with patients with severe renal dysfunction and patients with impaired hepatic function.

Epilepsy

Like other antidepressants, paroxetine should be used with caution in patients with epilepsy.

Convulsive seizures

Frequency of convulsive seizures in patients taking paroxetine, is less than 0.1%. In the event of a seizure, paroxetine should be discontinued.

Electroconvulsive therapy

There is only limited experience in the simultaneous use of paroxetine and electroconvulsive therapy.

Glaucoma

Like other SSRIs, paroxetine causes mydriasis, and it should be used with caution in patients with closed-angle glaucoma.

Hyponatremia

In the treatment of paroxetine, hyponatremia occurs rarely and predominantly in elderly patients and is leveled after the withdrawal of paroxetine. '

Bleeding

Hemorrhages in the skin and mucous membranes (including gastrointestinal bleeding) have been reported in patients with paroxetine. therefore paroxetine Caution should be used with caution in patients who simultaneously receive drugs that increase the risk of bleeding in patients with a known tendency to bleeding and patients with diseases predisposing to bleeding.

Heart Disease

In the treatment of patients with heart disease, the usual precautionary measures should be observed.

Symptoms that may occur when paroxetine is discontinued adults:

As a result of clinical studies in adults, the incidence of adverse events with paroxetine withdrawal was 30%, while the incidence of adverse events in the placebo group was 20%.

Describing withdrawal symptoms such as dizziness, sensory disturbances (including paresthesia, electric shock and tinnitus), sleep disorders (including bright dreams), agitation or anxiety, nausea, tremors, confusion, sweating, headaches and diarrhea are described. Usually these symptoms are mild or moderate, but in some patients they can be severe. Usually they occur in the first few days after the drug is discontinued, but in rare cases they occur in patients who accidentally missed only one dose.As a rule, these symptoms pass spontaneously and disappear within 2 weeks, but in some patients they can last much longer (2-3 months or more). It is recommended to reduce the dose of paroxetine gradually, for several weeks or months before its complete cancellation, depending on the needs of the individual patient.

The onset of withdrawal symptoms does not mean that the drug is abused or addictive, as is the case with drugs and psychotropic substances.

Fractures of bones

Based on the results of epidemiological studies of the risk of bone fractures, bone fragility was associated with the intake of antidepressants, including the SSRI group. The risk was observed during the course of treatment with antidepressants and was the maximum at the beginning of the course of therapy. The possibility of bone fractures should be considered when administering paroxetine.

Tamoxifen

Some studies have shown that the effectiveness of tamoxifen, measured as the ratio of breast cancer recurrence / mortality, decreases with co-administration with paroxetine, as a result of irreversible inhibition CYP2D6. Risk can increase with a joint appointment for a long time.When treating or preventing breast cancer, consideration should be given to the use of alternative antidepressants that do not affect CYP2D6 or act to a lesser extent.

Although paroxetine Does not increase the negative effect of alcohol on psychomotor functions, it is not recommended to apply simultaneously paroxetine and alcohol.

Effect on the ability to drive transp. cf. and fur:

Clinical experience with paroxetine indicates that it does not impair cognitive and psychomotor functions. However, as with any other psychotropic medications, patients should be especially cautious when driving a car and working with mechanisms.

Form release / dosage:

The tablets covered with a film cover of 20 mg.

For 10 tablets, film-coated, in a contour mesh package.

3 contour squares, together with instructions for use, are placed in a cardboard box.

Packaging:(10) - packings of cellular contour (1000) - boxes
(10) - packings, cellular, outline (3) - packs, cardboard

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001782

Date of registration:23.11.2011

The owner of the registration certificate:REPLEK FARM Skopje, OOOREPLEK FARM Skopje, OOO Macedonia

Manufacturer: & nbsp

REPLEK FARM SCOPE, LLC Russia

Representation: & nbspREPLECK FARM LTD SCOPJEREPLECK FARM LTD SCOPJERussia

Information update date: & nbsp20.08.2015

Illustrated instructions

Instructions

Paroxetine (Paroxetine)