Expiration date: 05/2025

Structure and Composition:

Film-coated tablets. 1 tablet contains Paroxetine 20 or 30 mg

(in the form of 22,760 or 34.140 mg of paroxetine hydrochloride hemihydrate, respectively)

Excipients: calcium hydrogen phosphate dihydrate, sodium starch glycolate (type A) magnesium stearate Hypromellose

composition of the shell: hypromellose, Macrogol 400 Macrogol 6000 Polysorbate 80 Titanium dioxide col. Code: 77891, E171

in blisters of 10 pieces. in a stack of cardboard 3 packaging.

Description pharmaceutical form:

Tablets 20 mg: white or almost white round film-coated tablets. On one side - the risk, on the other engraved «X20».

Tablets 30 mg: white or almost white, round, convex film-coated tablets of about 11 mm in diameter. On one side - the risk, on the other engraved "X30".

Pharmacokinetics:

After oral administration of paroxetine is well absorbed. It is metabolized in the liver to inactive metabolites. Simultaneous food intake does not affect the absorption and pharmacokinetics of paroxetine. Associated with the plasma protein to 93-95%. T1 / 2 is the average of paroxetine night. Dynamic balance is achieved in the blood plasma after 7-14 days after initiation of therapy in the future pharmacokinetics unchanged during prolonged therapy. Approximately 64% of paroxetine is excreted in the urine (2% as unchanged, 62% as metabolites), approximately 36% is allocated through the gastrointestinal tract, mainly in the form of metabolites, less than 1% is excreted in the feces unchanged.

The concentration of paroxetine in plasma increases with abnormal liver and kidney function, as well as in the elderly.

Description of the pharmacological actions:

Inhibits reverse neuronal uptake of serotonin in the central nervous system. Little effect on the neuronal uptake of norepinephrine and dopamine. It has also anxiolytic and psychoactive properties.

Testimony:

Treatment, including anti-relapse:

• Depression of various etiologies, including state accompanied by anxiety
  
• obsessive-compulsive disorder (obsessions syndrome)
  
• panic disorder, including with the fear of staying in a crowd (agoraphobia)
  
• social phobia
  
• post-traumatic stress disorder.
  

Contraindications:

• increased sensitivity to the drug in history
  
• therapy MAO inhibitors and the period after cessation of treatment MAO inhibitors within 2 weeks
  
• pregnancy
  
• breastfeeding
  
• Children up to age 18 years (due to lack of clinical experience).
  

Application of pregnancy and breastfeeding:

The safety of paroxetine during pregnancy has not been studied, so it should not be used during pregnancy and lactation, except when medically potential benefit of treatment exceeds potential risks associated with taking the drug.

Side effect:

The incidence of side effects and intensity of treatment is reduced in the process, so their development in most cases possible to continue taking the drug.

On the part of the digestive tract: nausea (12%), occasional constipation, diarrhea, loss of appetite rare - increase in liver function tests (a causal association between paroxetine and changes in liver enzyme activity is not proven, but in the case of abnormal liver function is recommended discontinuation of paroxetine) sometimes - severe hepatic dysfunction.

CNS: drowsiness (9%), tremor (8%), general weakness and fatigue (7%), insomnia (6%), in some cases - headache, irritability, paresthesia, dizziness, sleepwalking is rarely observed extrapyramidal disorders (observed predominantly with previous intensive use of neuroleptics) and orofacial dystonia. Rarely - epileptiform seizures (characterized therapy and other antidepressants) increased intracranial pressure.

From the senses: in some cases - blurred vision, mydriasis rarely - an attack of acute glaucoma.

Cardio-vascular system: in some cases - tachycardia, ECG changes, labile blood pressure, fainting.

From the genital and urinary system: ejaculation disorder (13%) in certain cases - changes in libido, rarely - difficulty urinating.

Electrolyte imbalance: in some cases - hyponatremia with the development of peripheral edema, impaired consciousness or epileptiform symptoms (most of these cases occurred in elderly patients who, in addition to paroxetine received diuretics and other drugs, in some cases, this condition develops as a result of overproduction of ADH after cancellation the drug in the blood sodium level normalized).

Dermatologic reactions and hypersensitivity reactions: rarely - skin redness, bruising, swelling in the face and extremities, anaphylactic reactions (urticaria, bronchospasm, angioedema), itchy skin.

Other: in rare cases - myopathy, myalgia, hyperglycaemia rarely - hyperprolactinemia, galactorrhea, hypoglycemia, fever and flu-like development of the state. Rarely - thrombocytopenia (causal relationship with the administration of the drug has not been proven) increase or decrease in body weight. Described several cases of excessive bleeding (see. "Precautions").

Sudden withdrawal of the drug may cause dizziness, sensory disturbances (eg paraesthesia), anxiety, sleep disturbances, agitation, tremor, nausea, sweating, and confusion, so the termination of drug therapy must be carried out gradually, it is advisable to reduce the dosage every second day.

Drug Interactions:

Food, antacids: food and antacids do not affect the absorption and pharmacokinetics of paroxetine.

MAO Inhibitors: like other inhibitors of serotonin reuptake, in animal studies reported adverse interaction between paroxetine and MAO inhibitors (See "Safety precautions.").

Tryptophan: in patients with concomitant use of paroxetine and tryptophan were marked by headache, nausea, sweating and dizziness, so you should avoid joint use of paroxetine and tryptophan.

Warfarin: between paroxetine and warfarin is expected pharmacodynamic interaction (with the unmodified prothrombin time marked by increased bleeding), so you need to paroxetine with extreme caution in patients receiving oral anticoagulants.

Sumatriptan: In a few cases, the combined use of marked weakness, hyperreflexia, incoordination. If necessary, the simultaneous use of sumatriptan and selective serotonin reuptake inhibitor latter should be implemented under strict medical supervision.

Benzodiazepines (oxazepam), barbiturates, antipsychotics: in the combined use of paroxetine and said data means to strengthen their inherent sedation (sleepiness) were observed. There is little experience of the combined use of paroxetine with neuroleptics, so in these cases should be used with caution (see "Side effects: extrapyramidal disorders.").

Tricyclic antidepressants (TCAs): as in the joint application of the other serotonin reuptake inhibitors with tricyclic antidepressants, caution is necessary, because paroxetine may inhibit TCA metabolism, carried out with the participation of isoenzyme SYR2D6. Therefore dose tricyclic antidepressants should be reduced (see. The combined use of drugs that induce and inhibit the metabolic enzyme system).

Lithium: sufficient experience joint application with lithium or paroxetine with other serotonin reuptake inhibitors have not yet been accumulated, so should be used with caution, under regular supervision of lithium levels in the blood.

The combined use of drugs that induce and inhibit the metabolic enzyme system: drugs that enhance or inhibit the activity of the liver enzyme systems that can affect the metabolism and pharmacokinetics of paroxetine. In a joint application with inhibitors of liver metabolic enzymes necessary to use the lowest effective dose of paroxetine. The combined use of inducers of liver enzymes does not require correction of the initial dose of paroxetine further change the dosage depends on the clinical effect (efficacy and tolerability).

The drugs, the metabolism of which is carried out with the participation of isoenzyme SYR2D6: paroxetine significantly inhibits the activity of isoenzyme SYR2D6. Therefore, special care needs of its simultaneous use with drugs whose metabolism occurs with the participation of isoenzyme, incl .: some antidepressants (such as nortriptyline, amitriptyline, imipramine, desipramine and fluoxetine), phenothiazines (such as thioridazine), antiarrhythmic drugs of the IC ( such as propafenone, flecainide and encainide), or which block its action (such as quinidine, cimetidine, codeine).

The drugs, the metabolism of which is carried out with the participation of isoenzyme SYRZA4: reliable clinical data on paroxetine isoenzyme inhibition SYRZA4 not, so with drugs that inhibit this enzyme (eg terfenadine), the application is likely to be permitted.

Cimetidine: cimetidine inhibits cytochrome P450 isozymes some consequence in the combined use increases the level of paroxetine concentrations in plasma at the stage of dynamic equilibrium.

Phenobarbital: Phenobarbital increases the activity of certain isoenzymes of cytochrome P450. When the joint application decreases the concentration of paroxetine in blood plasma, as well as shorter T1 / 2.

Anticonvulsants (phenytoin): at joint use of paroxetine and phenytoin decreases the concentration of paroxetine in blood plasma, however, may increase the frequency of side effects of phenytoin (the same is happening in the combined use of other anticonvulsants). In patients with epilepsy treated with long-term carbamazepine, phenytoin, or sodium valproate, the additional appointment of paroxetine did not cause changes in the pharmacokinetic and pharmacodynamic properties of anticonvulsants increase paroxysmal seizure were noted.

Drugs that bind to plasma proteins: paroxetine largely bound to plasma proteins. In an application with drugs, which also bind to plasma proteins, amid increasing paroxetine plasma concentrations may increase side effects.

Digoxin: because sufficient clinical experience of the combined use is not available, it is recommended to be careful in their simultaneous application.

Diazepam: Diazepam with exchange application does not affect the pharmacokinetics of paroxetine.

Procyclidine: paroxetine protsiklidina significantly increases the concentration in plasma, so the appearance of anticholinergic side effects should be reduced dose protsiklidina.

Beta-blockers: in clinical trials of paroxetine did not affect the level of propranolol in the blood.

Theophylline in some cases was an increase in the concentration of theophylline in blood.

Despite the fact that in the course of clinical studies, the interaction between paroxetine and theophylline is not proven, it is recommended regular monitoring of theophylline in the blood.

Alcohol: Alcohol strengthening action while the use of paroxetine has not been identified. However, due to the effect of paroxetine on the liver enzyme system, it is necessary to exclude the use of alcoholic beverages during treatment with paroxetine.

Dosage and administration:

Inside, 1 times a day, preferably in the morning, while eating, not chewing.

As with other antidepressant therapy, depending on the clinical condition of the patient after 2-3 weeks the dosage can be modified.

When depression: The recommended daily dose is 20 mg. As with other antidepressant effect in most cases it develops slowly. Some patients may need to increase the dose. Depending on the patient's response to therapy, the daily dose may be increased to 10 mg at intervals of one week to achieve a therapeutic effect with a maximum daily dose of 50 mg.

With obsessive-compulsive disorder (obsessions syndrome): starting dose is 20 mg / day. The dose may be increased by 10 mg weekly to achieve the desired therapeutic response. The maximum daily dose is usually 40 mg, but should not exceed 60 mg.

When panic disorder: The recommended therapeutic dose is 40 mg per day. Therapy should be initiated with a small (10 mg daily) dose increased with weekly doses of 10 mg per day, to achieve the desired effect. The maximum daily dose should not exceed 60 mg. The recommended initial dose is low due to the possibility of a temporary increase of the intensity of the symptoms at the start of therapy.

In social phobia: therapy can be initiated with a dose of 20 mg per day. If after two weeks of treatment, no significant improvement in the condition of the patient, the dose can be increased by 10 mg weekly until the desired effect. The maximum daily dose should not exceed 50 mg. For maintenance therapy is usually sufficient daily dose of 20 mg.

In post-traumatic stress disorder: The recommended therapeutic dose is 20 mg per day. Depending on the patient's response to therapy, the daily dose can be periodically increased to 10 mg, the maximum daily dose is 50 mg.

Depending on the clinical condition of the patient, to prevent the possibility of recurrence is necessary supportive therapy. This course after the disappearance of symptoms of depression may reach 4-6 months, and for panic disorder and obsessive or more. As with other psychotropic drugs, should avoid abrupt discontinuation of treatment (see. "Side effects"). In frail and elderly patients may increase above the normal level of the drug in the blood serum, therefore recommended starting dose is 10 mg per day. This dose can be increased by 10 mg weekly, depending on the patient.

The maximum dose should not exceed 40 mg per day.

Children due to lack of clinical experience with the drug is not shown.

When kidney (Cl creatinine <30 mL per minute) or liver failure increases the concentration of paroxetine in blood plasma, however the recommended daily dose in these cases is 20 mg. This dose may be increased depending on the patient's condition, but you must strive to maintain as low as possible.

Overdose:

Treatment with paroxetine is safe in a wide range of doses. Symptoms of overdose manifest when one-stage application of 2000 mg of paroxetine or receiving a large dose of paroxetine with other drugs or with alcohol.

Symptoms include nausea, vomiting, tremors, dilated pupils, dry mouth, general excitement, sweating, drowsiness, dizziness, redness of the skin. It was marked coma or convulsions. Fatal outcome in this case is rare, usually with simultaneous overdose (causing adverse interactions) paroxetine and another drug.

Treatment: should ensure that clearing the airway, if necessary - oxygenation, gastric lavage or induction of vomiting, intake of 20-30 grams of activated charcoal every 4-6 hours during the first 24-48 hours is recommended constant monitoring of the heart and other vital functions.. Forced diuresis, hemodialysis or hemoperfusion are ineffective if a large dose of paroxetine came from the blood into the tissues. No specific antidote.

Precautionary measures:

Contraindications receiving paroxetine simultaneously with MAO inhibitors and within 2 weeks after their withdrawal. In the future, paroxetine should be used with extreme caution, since treatment with small doses and gradually increasing the dosage to achieve the desired therapeutic effect. After treatment with paroxetine for 2 weeks can not start a course of treatment MAO inhibitors.

Have a history of mania: how and when taking other antidepressants, if the patient has previously been in a manic state, while taking paroxetine should be considered the possibility of occurrence of relapse.

Cardiovascular system: with impaired function of the cardiovascular system of the drug should be used with caution.

Epilepsy: paroxetine, as well as other antidepressants, should be used with caution in the presence of a history of epilepsy. According to clinical observations, paroxetine in 0.1% of patients causes epileptiform seizures. It is necessary to interrupt the treatment of patients who have manifested such disorders.

Electroconvulsive therapy (ECT): there is not enough experience of the simultaneous use of ECT therapy and paroxetine.

In the treatment of patients with depression and drug addiction in the withdrawal phase should be closely monitored for these patients because of their predisposition to suicidal attempts.

Hyponatremia: in some cases has been noted hyponatremia, especially in elderly patients receiving diuretics. After the abolition of paroxetine in blood sodium levels to normal.

Increased bleeding: In some cases, during treatment with paroxetine occurred bleeding (mostly ecchymosis and purpura).

Glaucoma as other selective serotonin reuptake inhibitor, paroxetine cause mydriasis, so the presence of glaucoma used with caution.

Rarely observed hyperglycemic condition while taking paroxetine.

Special instructions:

Apply strictly prescribed by a doctor to avoid complications.

Women of childbearing age during treatment with paroxetine contraception is recommended.

Studies have found no adverse effects of paroxetine on psychomotor or cognitive function. Despite this, at the beginning of a course of therapy for individual deadline can not drive a car or work in a high-risk, requiring a quick response.