Paxil, pills 20mg, 30pcs

Composition

Active ingredient:  

paroxetine hydrochloride hemihydrate 22.8 mg (equivalent to 20.0 mg of paroxetine);

Auxiliary substances:

calcium dihydrogen phosphate dihydrate;

sodium carboxymethyl starch type A;

magnesium stearate;

Tablet shell:

Opadry white YS-1R-7003 (hypromellose, titanium dioxide, macrogol 400, polysorbate 80);

Pharmacological action

Paxil-antidepressant activity is caused by specific inhibition of serotonin reuptake in brain neurons.

Pharmacodynamics

It has a low affinity for muscarinic cholinergic receptors, and animal studies have shown that anticholinergic properties are poorly expressed. In vitro studies have shown that paroxetine has a weak affinity for alpha-1, alpha –_2, and beta-adrenergic receptors, as well as for dopamine (_D2), serotonin 5-HT1, and 5 – HT2, and histamine (_H1) receptors.

The absence of interaction with postsynaptic receptors in vitro is confirmed by the results of in vivo studies that demonstrated the absence of paroxetine’s ability to depress the central nervous system and cause arterial hypotension. It does not interfere with psychomotor functions and does not increase the depressing effect of ethanol on the central nervous system.

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

Studies of EEG behavior and changes have shown that paroxetine produces weak activating effects at doses higher than those required to inhibit serotonin reuptake. By its nature, its activating properties are not amphetamine-like.

Animal studies have shown that paroxetine does not affect the cardiovascular system.

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

Pharmacokinetics

When taken orally, it is well absorbed and undergoes metabolism during the” first pass ” through the liver. Due to first-pass metabolism, less paroxetine enters the systemic circulation than is absorbed from the gastrointestinal tract. As the amount of paroxetine in the body increases with a single large dose or with repeated use of conventional doses, partial saturation of the “first pass” metabolic pathway occurs and the clearance of paroxetine from plasma decreases.

This leads to a disproportionate increase in plasma concentrations of paroxetine. Therefore, its pharmacokinetic parameters are unstable, resulting in nonlinear kinetics. It should be noted, however, that non-linearity is usually poorly expressed and is observed only in those patients who have low plasma levels of paroxetine against the background of taking low doses of the drug. Steady-state plasma concentrations are reached after 7-14 days.

Paroxetine is widely distributed in tissues, and pharmacokinetic calculations show that only 1% of the total amount of paroxetine present in the body remains in plasma. At therapeutic concentrations, approximately 95% of plasma paroxetine is bound to proteins. No correlation was found between the plasma concentrations of paroxetine and its clinical effect (adverse reactions and efficacy). It was found that paroxetine in small amounts penetrates into the breast milk of women, as well as into the embryos and fetuses of laboratory animals.

Biotransformes into inactive polar and conjugated products (oxidation and methylation processes). T_1/2 varies, but is usually about one day (16-24 hours). About 64% is excreted in the urine as metabolites, less than 2% – unchanged; the remaining amount is excreted in the feces (probably entering it with bile) as metabolites, less than 1% – unchanged. The elimination of metabolites is biphasic, including primary metabolism (first phase) and systemic elimination.

Indications

• Depression of all types in adults, including reactive and severe depression, as well as depression accompanied by anxiety;
• OCD in adults (including as a means of support and preventive therapy), as well as in children and adolescents 7-17 years;
• panic disorder in adults with agoraphobia and without it (including as a means of support and preventive therapy;
• social phobia in adults (including as a means of support and preventive therapy), as well as in children and adolescents aged 8-17 years;
• generalized anxiety disorder in adults (including as a means of support and preventive therapy);
• post-traumatic stress disorder in adults.

Use during pregnancy and lactation

Pregnancy

Animal studies have not shown any teratogenic or selective embryotoxic activity in paroxetine, and data on a small number of women who took paroxetine during pregnancy indicate that there is no increased risk of congenital anomalies in newborns.

Preterm birth has been reported in women who received paroxetine or other SSRI medications during pregnancy, but a causal relationship between these medications and preterm birth has not been established. Paroxetine should not be used during pregnancy if its potential benefit does not exceed the possible risk.

Special attention should be paid to the health status of those newborns whose mothers took paroxetine in late pregnancy, as 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, a causal relationship between the mentioned complications and this drug therapy has not been established. The clinical complications described included: respiratory distress, cyanosis, apnea, seizures, body temperature instability, difficulty feeding, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, tremor, irritability, lethargy, constant crying, and drowsiness.

In some reports, the symptoms were described as neonatal manifestations of withdrawal syndrome. In most cases, the described complications occurred immediately after delivery or shortly after it (

Lactation

A small amount of paroxetine penetrates into breast milk. However, paroxetine should not be taken during breastfeeding unless its benefits to the mother outweigh the potential risk to the baby.

Contraindications

Hypersensitivity to paroxetine and its components.

Concomitant use of paroxetine with MAO inhibitors (paroxetine should not be used simultaneously with MAO inhibitors or for 2 weeks after their withdrawal; MAO inhibitors should not be prescribed for 2 weeks after discontinuation of paroxetine treatment).

Combined use with thioridazine (paroxetine should not be administered in combination with thioridazine, since, like other drugs that inhibit the activity of the cytochrome P450 CYP2D6 enzyme, paroxetine can increase the concentration of thioridazine in plasma).

Side effects

Disorders of the blood and lymphatic system:  sometimes-abnormal bleeding, mainly hemorrhage in the skin and mucous membranes (most often bruising); very rarely — thrombocytopenia.

Immune system disorders:  very rarely — allergic reactions (including urticaria and angioedema).

Endocrine disorders:  very rarely — the syndrome of impaired ADH secretion.

Metabolic disorders:  often-decreased appetite; rarely-hyponatremia (occurs mainly in elderly patients and may be due to the syndrome of impaired ADH secretion).

Mental disorders:  often — drowsiness, insomnia; sometimes-confusion, hallucinations; rarely-manic reactions. These symptoms may also be caused by the disease itself.

Visual disturbances:  often — blurred vision; very rarely-exacerbation of glaucoma.

Cardiac disorders:  sometimes-sinus tachycardia.

Vascular disorders:  sometimes-a transient increase or decrease Blood pressure, including in patients with pre-existing hypertension or anxiety.

Respiratory, thoracic and mediastinal disorders:  often — yawning.

Nervous system disorders:  often — convulsive seizures.

Gastrointestinal disorders:  very often — nausea; often-constipation, diarrhea, dry mouth; very rarely-gastrointestinal bleeding.

Hepatobiliary disorders:  rarely-elevated liver enzymes; very rarely-hepatitis, sometimes accompanied by jaundice and / or liver failure. Sometimes there is an increase in liver enzyme levels. Post-marketing reports of liver damage such as hepatitis, sometimes with jaundice, and / or liver failure are very rare. The question of whether to discontinue treatment with paroxetine should be addressed in cases where there is a long-term increase in liver function tests.

Skin and subcutaneous tissue disorders: often — sweating; rarely-skin rashes; very rarely-photosensitivity reactions.

Kidney and urinary tract disorders: rarely-urinary retention.

Disorders of the reproductive system and mammary glands: very often — sexual dysfunction; rarely-hyperprolactinemia/galactorrhea.

General violations: often-asthenia; very rarely-peripheral edema.

Symptoms that occur when paroxetine treatment is discontinued: often — dizziness, sensory disturbances, sleep disturbances, anxiety, headache; sometimes-agitation, nausea, tremor, confusion, sweating, diarrhea.

Interaction

Serotonergic drugs. The use of paroxetine, as well as other SSRI drugs, simultaneously with serotonergic drugs (including MAO inhibitors, L-tryptophan, triptans, tramadol, linezolid, other SSRI drugs, lithium and herbal products containing St. John’s wort) may be accompanied by the development of serotonin-related effects. Caution should be exercised when using these drugs in combination with paroxetine and close clinical monitoring should be performed.

Enzymes involved in drug metabolism. The metabolism and pharmacokinetics of paroxetine may change under the influence of induction or inhibition of enzymes that are involved in drug metabolism. When using paroxetine concomitantly with inhibitors of enzymes involved in drug metabolism, the feasibility of using a paroxetine dose that is in the lower part of the therapeutic dose range should be evaluated.

The initial dose of paroxetine does not need to be adjusted if it is used simultaneously with a drug that is a known inducer of enzymes involved in drug metabolism (for example, carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent dose adjustment of paroxetine should be determined by its clinical effects (tolerability and efficacy).

CYP3A4. An in vivo interaction study with concomitant steady-state use of paroxetine and terfenadine, which is a substrate of the CYP3A4 enzyme, showed that paroxetine does not affect the pharmacokinetics of terfenadine. In a similar in vivo interaction study, no effect of paroxetine on the pharmacokinetics of alprozalam and vice versa was found. Concomitant use of paroxetine with terfenadine, alprozalam and other drugs that serve as a substrate for the enzyme CYP3A4 is unlikely to cause harm to the patient.

The ability of paroxetine to inhibit the CYP2D6 enzyme (see also “Contraindications”). Like other antidepressants, including other SSRIs, paroxetine inhibits the liver enzyme CYP2D6, which belongs to the cytochrome P450 system. Inhibition of the CYP2D6 enzyme can lead to an increase in plasma concentrations of concomitantly used drugs that are metabolized by this enzyme. These medications include tricyclic antidepressants (such as amitriptyline, nortriptyline, imipramine, and desipramine), phenothiazine-type neuroleptics, risperidone, certain type 1C antiarrhythmics (such as propafenone and flecainide), and metoprolol.

Procyclidine. Daily intake of paroxetine significantly increases the plasma concentrations of procyclidine. If anticholinergic effects occur, the dose of procyclidine should be reduced.

Anticonvulsants: carbamazepine, phenytoin, sodium valproate. Concomitant use of paroxetine and these drugs does not affect their pharmacokinetics and pharmacodynamics in patients with epilepsy.

Clinical studies have shown that the absorption and pharmacokinetics of paroxetine are independent or practically independent (i. e., the existing dependence does not require a dose change) from food intake, antacids, digoxin, propranolol, alcohol.

How to take, course of use and dosage

Inside (the tablet should be swallowed whole, without chewing),1 time a day (in the morning, during meals).

Depression. The recommended dose for adults is 20 mg per day, if necessary, depending on the therapeutic effect, the dose can be increased weekly by 10 mg per day, with a maximum daily dose of 50 mg. As with any antidepressant treatment, the effectiveness of therapy should be evaluated and, if necessary, the dose of paroxetine should be adjusted 2-3 weeks after the start of treatment and further depending on the clinical indications.

To stop depressive symptoms and prevent relapses, it is necessary to observe an adequate duration of relief and maintenance therapy. Use of paroxetine in children and adolescents (7-17 years) it is not recommended for the treatment of depression due to the lack of data on the effectiveness of therapy.

Obsessive-compulsive disorder. The recommended dose for adults 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 an adequate duration of therapy. For children and adolescents (7-17 years), the initial dose is 10 mg per day, it can be increased weekly by 10 mg per day. If necessary, the dose can be increased to 50 mg per day.

Panic disorder. The recommended dose for adults 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 can be increased to 60 mg per day. A low initial dose is recommended to minimize the possible increase in symptoms of panic disorder that may occur at the beginning of treatment with any antidepressants. It is necessary to observe adequate terms of therapy.

Social phobia. The recommended dose for adults is 20 mg per day. If necessary, the dose can be increased weekly by 10 mg per day, depending on the clinical effect-up to 50 mg per day. Treatment of children and adolescents (8-17 years) should start with a dose of 10 mg per day and increase the dose weekly by 10 mg per day, focusing on the clinical effect. If necessary, the dose can be increased to 50 mg per day.

Generalized anxiety disorder. The recommended dose for adults is 20 mg per day. If necessary, the dose can be increased weekly by 10 mg per day, depending on the clinical effect-up to 50 mg per day.

Post-traumatic stress disorder. The recommended dose for adults is 20 mg per day. If necessary, the dose can be increased weekly by 10 mg / day, depending on the clinical effect-up to 50 mg per day.

Overdose

Symptoms: in addition to the symptoms described in the “Side effects” section, there is vomiting, dilated pupils, fever, and a change in blood pressure. Blood pressure, involuntary muscle contractions, agitation, anxiety, tachycardia.

Patients ‘ condition usually returned to normal without serious consequences, even with a single dose of up to 2000 mg. A number of reports describe symptoms such as coma and changes ECG; deaths were very rare, usually in situations where patients were taking paroxetine together with other psychotropic drugs or with alcohol.

Treatment: general measures used in case of overdose of any antidepressants; if necessary, gastric lavage, use of activated charcoal (20-30 mg every 4-6 hours during the first day after overdose), maintenance therapy and frequent monitoring of the main physiological parameters.

There is no specific antidote for paroxetine.

Special instructions

Withdrawal of paroxetine. Withdrawal symptoms such as dizziness, sensory disturbances (including paresthesia and electric shock sensations), sleep disturbances (including vivid dreams), agitation and anxiety, nausea, tremor, confusion, sweating, headaches and diarrhea are described. These symptoms are usually mild to moderate, but may be severe in some patients. They usually occur in the first few days after discontinuation of the drug, but in rare cases they occur in patients who accidentally missed taking just one dose. As a rule, these symptoms resolve spontaneously and disappear within 2 weeks, but in some patients they can last much longer (2-3 months or more).

As with other psychotropic medications, abrupt withdrawal of paroxetine should be avoided. The following cancellation scheme can be recommended: reduction of the daily dose by 10 mg at weekly intervals; after reaching a dose of 20 mg/day (or 10 mg/day in children and adolescents), patients continue to take this dose for 1 week and only after that the drug is completely discontinued.

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

The occurrence of withdrawal symptoms does not mean that the drug is an object of abuse or dependence, as is the case with drugs and psychotropic substances.

Symptoms that may occur when paroxetine treatment is discontinued in children and adolescents. Symptoms of paroxetine withdrawal (emotional lability, incl. suicidal thoughts, suicidal attempts, mood changes and tearfulness, as well as nervousness, dizziness, nausea and abdominal pain) were recorded in 2% of patients with a reduction in the dose of paroxetine or after its complete withdrawal and occurred 2 times more often than in the placebo group.

Individual patient groups.

Elderly patients. In elderly patients, plasma concentrations of paroxetine may be elevated, but the range of concentrations coincides with those in younger patients. In this category of patients, therapy should begin with the recommended dose for adults, which can be increased to 40 mg / day.

Patients with impaired renal or hepatic function. Plasma concentrations of paroxetine are elevated in patients with severe renal impairment (creatinine clearance < 30 ml / min) and in patients with impaired liver function. Such patients should be prescribed doses of the drug that are in the lower part of the therapeutic dose range.

Children under 7 years old. The use of paroxetine is not recommended due to the lack of studies on the safety and effectiveness of the drug in this group of patients.

Children and teenagers aged 7-17. In clinical trials, adverse events related to suicidality (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, deviant behavior, and anger) were more common in children and adolescents treated with paroxetine than in those in this age group who received placebo. Currently, there are no data on the long-term safety of paroxetine for children and adolescents, which would relate to the effect of this drug on growth, maturation, cognitive and behavioral development.

Clinical deterioration and suicidal risk associated with psychiatric disorders. Patients with depression may experience an exacerbation of symptoms of this disorder and / or the appearance of suicidal thoughts and behavior (suicidality) regardless of whether they receive antidepressants. This risk persists until a pronounced remission is achieved. The patient’s condition may not improve in the first weeks of treatment or more, so the patient should be closely monitored for 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 all antidepressants shows that the risk of suicide may increase in the early stages of recovery.

Other psychiatric disorders that paroxetine is used to treat may also be associated with an increased risk of suicidal behavior. In addition, these disorders may be comorbid conditions associated with major depressive disorder. Therefore, when treating patients suffering from other mental disorders, the same precautions should be taken as in the treatment of major depressive disorder.

Patients who have a history of suicidal behavior or suicidal thoughts, young patients, and patients with severe suicidal thoughts before starting treatment are most at risk of suicidal thoughts or attempts, so they all need to be given special attention during treatment.

Patients (and their caregivers) should be warned to monitor their condition for deterioration and/or the appearance of suicidal thoughts / suicidal behavior or thoughts of self-harm, and if these symptoms occur, seek immediate medical attention.

Akathisia. Occasionally, treatment with paroxetine or another SSRI medication is accompanied by akathisia, which is manifested by a feeling of internal anxiety and psychomotor agitation, when the patient cannot sit or stand still; with akathisia, the patient usually experiences subjective distress. Akathisia is most likely to occur in the first few weeks of treatment.

Serotonin syndrome/neuroleptic malignant syndrome. In rare cases, serotonin syndrome or symptoms similar to neuroleptic malignant syndrome may occur during treatment with paroxetine, especially if paroxetine is used in combination with other serotonergic drugs and/or neuroleptics.

These syndromes are potentially life-threatening, so if they occur, paroxetine treatment should be discontinued (they are characterized by a combination 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 start supportive symptomatic therapy. Paroxetine should not be given in combination with such serotonin precursors as L-tryptophan, oxy-triptan due to the risk of 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 mixed / manic episode in patients at risk for bipolar disorder.

Prior to starting treatment with an antidepressant, a thorough screening should be conducted to assess the patient’s risk of bipolar disorder; such screening should include collecting a detailed psychiatric history, including family history of suicide, bipolar disorder, and depression. Like all antidepressants, paroxetine is not registered for the treatment of bipolar depression. Paroxetine should be used with caution in patients with a history of mania.

MAO inhibitors. 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 the optimal therapeutic effect is achieved (see also “Contraindications”).

Impaired renal or hepatic function. Caution is recommended when treating patients with severe renal impairment and patients with hepatic impairment with paroxetine.

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

Convulsive seizures. The frequency of seizures in patients taking paroxetine is less than 0.1%. If a seizure occurs, treatment with paroxetine should be discontinued.

Electroconvulsive therapy. There is limited experience with concomitant use of paroxetine and electroconvulsive therapy.

Glaucoma. Like other SSRIs, paroxetine rarely causes mydriasis and should be used with caution in patients with angle-closure glaucoma.

Hyponatremia. When treated with paroxetine, hyponatremia occurs rarely and mainly in elderly patients.

Bleeding. Skin and mucosal hemorrhages (including gastrointestinal bleeding) have been reported in patients treated with paroxetine. Therefore, paroxetine should be used with caution in patients who are receiving concomitant medications that increase the risk of bleeding, in patients with a known tendency to bleed, and in patients with diseases predisposing to bleeding.

Heart diseases. The usual precautions should be taken when treating patients with heart disease.

Clinical experience with paroxetine suggests that it does not impair cognitive and psychomotor functions. However, as with the treatment of any other psychotropic drugs, patients should be especially careful when driving a car and working with mechanisms.

Despite the fact that paroxetine does not increase the negative effect of alcohol on psychomotor functions, it is not recommended to use paroxetine and alcohol at the same time.

Tablet Form of production

Storage conditions

In a dry place, at a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Paroxetine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Depression, Phobias and Panic Attacks, Stress