REKSETIN

Active material: Paroxetine
When ATH: N06AB05
CCF: Antidepressant
ICD-10 codes (testimony): F31, F32, F33, F40, F41.0, F41.2, F42, F43
When CSF: 02.02.04
Manufacturer: GEDEON RICHTER Ltd. (Hungary)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated white or nearly white, round, lenticular, with Valium on one party and chasing “X20” – another.

Excipients: gipromelloza, calcium hydrogen phosphate dihydrate, sodium carboxymethyl starch, magnesium stearate.

The composition of the shell: gipromelloza, macrogol 400, macrogol 6000, polysorbate 80, Titanium dioxide.

10 PC. – blisters (3) – packs cardboard.

Pills, Film-coated white or nearly white, round, lenticular, with Valium on one party and chasing “X30” – another.

Excipients: gipromelloza, calcium hydrogen phosphate dihydrate, sodium carboxymethyl starch, magnesium stearate.

The composition of the shell: gipromelloza, macrogol 400, macrogol 6000, polysorbate 80, Titanium dioxide.

10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Antidepressant. It 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 stimulating effect.

Pharmacokinetics

Absorption

After oral administration of paroxetine is well absorbed from the gastrointestinal tract. Simultaneous food intake does not affect the absorption and pharmacokinetics of paroxetine.

Distribution

Paroxetine is bound to plasma proteins at 93-95%. The equilibrium state is achieved after 7-14 days after start of therapy, Later in the pharmacokinetics of long-term therapy is not changed.

Metabolism

It is metabolized primarily in the liver with the formation of active metabolites predominantly.

Deduction

T_1/2 paroxetine is in the range of 6 to 71 no, but averages 24 no. About 64% Paroxetine is excreted in urine (2% – in unchanged form, 62% – as metabolites); about 36% excreted through the intestines, mainly as metabolites, less 1% – unchanged in the feces.

Pharmacokinetics in special clinical situations

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

Testimony

- Depression of various etiologies, incl. states, accompanied by anxiety;

- Obsessive-compulsive disorders (obsessive-compulsive);

- Panic disorder, incl. the fear of staying in the crowd (agoraphobia);

- Sociofobii;

- Disorder generalized anxiety (GTR);

- Post-traumatic stress disorder.

It is also used as part of anti-treatment.

Dosage regimen

Tablets should be taken 1 time / day, preferably in the morning, while eating, without chewing.

As with other antidepressant therapy, depending on the clinical condition of the patient through 2-3 weeks of therapy the dose can be changed.

At depression The recommended daily dose is 20 mg. The effect develops more gradually. Some patients may increase the dosage. The daily dose can be increased by 10 mg per week to achieve a therapeutic effect; The maximum daily dose is 50 mg / day.

At obsessive-compulsive disorders (obsessive-compulsive) starting dose is 20 mg / day. The dose may be increased by 10 mg to achieve a therapeutic response. The maximum daily dose is, usually, 40 mg, but should not exceed 60 mg.

At panic disorders the recommended therapeutic dose is 40 mg / day. Therapy should start with a small (10 mg / day) dose, with a weekly increase of 10 mg per week until 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 of the disease at the beginning of therapy.

At sociofobiâh therapy can be initiated with a dose 20 mg / day. If after two weeks of treatment, no significant improvement in the patient's condition, the dose may be increased at weekly 10 mg to achieve the desired effect. The maximum daily dose should not exceed 50 mg. For maintenance therapy, the drug is used at a dose of 20 mg / day.

At generalized anxiety disorder the recommended therapeutic dose is 20 mg / day. Depending on the patient's response to therapy daily dose may be increased gradually 10 mg per week; the maximum daily dose – 50 mg.

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

Depending on the clinical condition of the patient to prevent the possibility of recurrence necessary to carry out maintenance therapy. Maintenance therapy after the disappearance of symptoms depression can make 4-6 Months, and when panic disorder and obsessive and more. As with other psychotropic drugs, Avoid abrupt discontinuation of therapy.

In debilitated patients and elderly paroxetine concentration in serum may increase faster than normal, therefore, the recommended starting dose is 10 mg / day. This dose can be increased by 10 mg weekly, depending on the condition of the patient. The maximum dose does not exceed 40 mg / day.

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

At kidney (CC< 30 ml / min) or hepatic insufficiency increasing the concentration of paroxetine in blood plasma, therefore recommended daily dose in these cases is 20 mg. This dose can be increased depending on the patient, but you must strive to maintain the dose to the lowest possible level.

Side effect

Adverse reactions are presented with a detection rate ratio of the total number of patients receiving this treatment.

From the digestive system: nausea (12%); sometimes – constipation, diarrhea, decreased appetite; rarely – increased rates of liver function tests; in some cases – severe liver dysfunction. Between paroxetine and changes in liver enzymes have not proven a causal link, but in the case of abnormal liver function is recommended discontinuation of paroxetine.

From the central and peripheral nervous system: drowsiness (9%); tremor (8%); weakness and fatigue (7%), insomnia (6%); in some cases – headache, irritability, paresthesia, dizziness, somnambulism, poor concentration; rarely – extrapyramidal disorders, orofacial dystonia. Extrapyramidal disorder observed primarily in the preceding intensive use of neuroleptics. Rarely observed epileptiform seizures (which is characteristic of other antidepressants and therapy); intracranial hypertension.

Since the autonomic nervous system: increased perspiration (9%), dry mouth (7%).

On the part of the organ of vision: in some cases – blurred vision, midriaz; rarely – attack of acute glaucoma.

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

On the part of the reproductive system: ejaculation disorder (13%), in some cases – changes in libido.

From the urinary system: rarely – difficulty urinating.

From the water-electrolyte balance: in some cases – hyponatremia with the development of peripheral edema, impaired consciousness or epileptiform symptoms. After discontinuation of the drug sodium levels in the blood to normal. In some cases, this condition develops as a result of overproduction of antidiuretic hormone. Most of these cases occurred in elderly persons, which in addition to paroxetine received diuretics and other medications.

Allergic reactions: rarely – dermahemia, subcutaneous hemorrhage, swelling of the face and extremities, anaphylactic reactions (hives, bronchospasm, angioedema), itching.

Other: in a few cases – myopathies, mialgii, myasthenia, myoclonus, giperglikemiâ; rarely – hyperprolactinemia, galactorrhea, gipoglikemiâ, fever and flu-like development of the state, change in taste. Rarely has developed thrombocytopenia (a causal relationship to drug intake is not proven). Paroxetine may be accompanied by an increase or decrease in body weight. Described several cases of excessive bleeding.

Paroxetine, compared with tricyclic antidepressants, less likely to cause dry mouth, constipation and drowsiness. Sudden withdrawal of the drug may cause dizziness, sensory disturbances (eg, paresthesia), a sense of fear, sleep disturbance, ažitaciû, tremor, nausea, sweating and confusion, so termination of drug therapy must be carried out gradually (it is advisable to reduce the dosage every other day).

The incidence of side effects and intensity during therapy decreases, therefore when their development in most cases possible to continue taking the drug.

Contraindications

- Simultaneous reception of MAO inhibitors and the period 14 days after their cancellation;

- Pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years (due to lack of clinical experience);

- Hypersensitivity to the drug.

Reksetin^® It should not be used in combination with thioridazine, because like other drugs, that inhibit the CYP2D6 isoenzyme, paroxetine may increase the plasma levels of thioridazine. Appointment of thioridazine can lead to a lengthening of the QT interval on an electrocardiogram associated with serious ventricular arrhythmias, such as torsades de pointes (twisting zhelulochkovaya tachycardia), and cause sudden death.

FROM caution use in patients with functional disorders of the cardiovascular system, hepatic insufficiency, chronic renal failure, prostatic hyperplasia, as well as in elderly patients.

Paroxetine should be used with caution in the presence of a history of epilepsy. According to clinical observations, paroxetine causes epileptiform seizures in 0.1% patients. It is necessary to interrupt the treatment of patients, who appeared like disorder.

Paroxetine vыzыvaet mydriasis, however the presence of glaucoma, should be used with caution.

In sovmestnom primenenii paroxetine with benzodiazepinami (oxazepam), ʙarʙituratami, neuroleptics data to strengthen their inherent sedation (drowsiness) not observed. There is little experience with joint use of paroxetine with neuroleptics, therefore in these cases should be used with caution.

Sufficient experience with the combined use of lithium or paroxetine with other serotonin reuptake inhibitors have not yet gained, therefore this combination should be used with caution, regularly monitor the level of lithium in the blood.

Pregnancy and lactation

The safety of paroxetine during pregnancy and lactation has not been studied, so the drug should not be used during pregnancy and lactation, except, when medically potential benefit of treatment exceeds potential risk, drug-related.

Women of childbearing age during paroxetine therapy is recommended contraception.

Cautions

Contraindications paroxetine simultaneously with MAO inhibitors and within 14 days after their cancellation. In the future, paroxetine should be used with extreme caution, starting treatment with a low dose and gradually increase the dosage until the desired therapeutic effect. After the end of treatment with paroxetine for 14 days can not start treatment MAO inhibitors.

If the patient has previously been in a manic state, while taking paroxetine should consider the possibility of relapse (as when receiving other antidepressants).

There is little experience of simultaneous use of electroconvulsive therapy and paroxetine.

In connection with the predisposition to suicide attempts in patients with depression and patients with drug addiction during abstinence for this group of patients should be closely monitored during treatment.

In many cases, there is hyponatremia, especially in elderly patients, who receive diuretics. After the cancellation of paroxetine sodium levels in the blood to normal.

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

Against the background of paroxetine rarely observed hyperglycemic state.

Suicide / suicidal ideation

Depression is associated with an increased risk of suicidal thoughts, autoaggression and suicide. This risk persists until, until there comes a remission. Since the improvement may not occur during the first few weeks or more from the start of treatment, patients should be carefully monitored, until such improvement will not happen. Existing clinical experience suggests, that with antidepressant, the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions, where appointed Reksetin^®, They can also be combined with an increased risk of suicidal behavior. Besides, These states may be associated in major depressive disorder. The same precautions, and that in patients with major depressive disorder, You must be respected, when it comes to treating patients with other psychiatric disorders. Patients with a history of suicidal behavior or thoughts, or demonstrating a significant degree of suicidal ideation prior to treatment, They are at greater risk of suicidal thoughts or suicide attempts, and must be carefully monitored during treatment. In such patients, aged 18-29 years, there is an increased risk of suicide, so drug treatment should be closely monitored.

Patients (they, who assists patients) We should be prepared for the need to control in an emergency – the emergence of suicidal ideation / behavior or thoughts of self-aggression, for, to seek medical advice immediately, If these symptoms are present.

Effects on ability to drive vehicles and management mechanisms

Controlled studies did not reveal any adverse effects of paroxetine on psychomotor or cognitive function. Despite this, at the beginning of therapy, for individually deadline, you can not drive a car or work in high-risk, requiring quick response. The degree of limitation is determined individually.

Overdose

Symptoms: paroxetine safe in a wide range of doses. Symptoms of overdose manifest in the use of paroxetine in a single-step dose 2000 mg or more other drugs, or with alcohol: nausea, vomiting, tremor, mydriasis, dry mouth, general excitement, increased perspiration, drowsiness, dizziness, redness of the skin. It was noted coma or convulsions. Fatal outcome in this case was marked by rare, In most simultaneous overdose and other drug paroxetine, causing adverse interactions.

Treatment: gastric lavage, 20-30 g of activated charcoal per 4-6 h during the first 24-48 no; should release the airways, if necessary, carry out oxygenation. Monitor vital body functions and common activities, aimed at maintaining them. It is recommended that continuous monitoring of the heart and other vital functions. No specific antidote. Forced diuresis, hemodialysis or hemoperfusion are ineffective, if a large dose of paroxetine came from the blood into the tissues.

Drug Interactions

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

Like other serotonin reuptake inhibitors, in animal studies reported adverse interaction between MAO inhibitors and paroxetine.

The simultaneous use of paroxetine with tryptophan leads to headache, nausea, sweating and dizziness, so you should avoid the use of this combination.

Between paroxetine and warfarin is expected pharmacodynamic interaction (if unaltered prothrombin time marked by increased bleeding); use of the combination requires caution.

In a joint application with paroxetine sumatriptan marked weakness, hyperreflexia, incoordination. If necessary, their simultaneous application requires special care (requires medical supervision).

With simultaneous use of paroxetine may inhibit the metabolism of tricyclic antidepressants (by inhibiting CYP2D6 isoenzyme), Therefore, the use of such a combination requires caution and reduce doses of tricyclic antidepressants.

Preparations, that enhance or inhibit the activity of the liver enzyme systems, may affect the metabolism and pharmacokinetics of paroxetine. In a joint application with the metabolic inhibitors of liver enzymes is necessary to use the smallest effective dose of paroxetine. The combined use of inducers of liver enzymes does not require correction of the initial dose of paroxetine; further change in dosage depends on the clinical effect (efficacy and tolerability).

Paroxetine significantly inhibits the activity of CYP2D6 isoenzyme. Therefore, special care requires the simultaneous use of paroxetine with drugs, metabolism that occurs with the participation of isoenzyme, incl. some antidepressants (eg, nortryptylyn, Amitriptyline, imipramine, fluoxetine and desipramine), fenotiazinami (eg, tioridazin), antiarrhythmic drugs class 1 C (eg, propafenone, flecainide and encainide) or those drugs, which block its action (eg, quinidine, cimetidine, codeine).

No reliable clinical data on paroxetine inhibit CYP3A4 No, therefore it is possible to use preparations, inhibit this enzyme (eg, terfenadine).

Cimetidine inhibits some cytochrome P450 isozymes. Consequently, when used together with cimetidine paroxetine paroxetine increased levels in the blood plasma in step equilibrium.

Phenobarbital increases the activity of some cytochrome P450 isoenzymes. In a joint application with phenobarbital paroxetine paroxetine reduced the concentration in the blood plasma, and shortened his T_1/2.

When combined use of paroxetine and phenytoin decreased the concentration of paroxetine in plasma and may increase the frequency of side effects of phenytoin. When using other anticonvulsants may also increase the frequency of side effects. Patients with Epilepsy, treated with carbamazepine for a long time, phenytoin, or sodium valproate, supplementation paroxetine did not cause changes in pharmacokinetic and pharmacodynamic properties of anticonvulsants; increasing paroxysmal seizure were noted.

Paroxetine largely bound to plasma proteins. In an application with drugs, which are also bound to plasma proteins, accompanied by increased concentration of paroxetine in blood plasma may increase side effects.

Due to the lack of sufficient clinical experience of joint use of digoxin with paroxetine appointment of such a combination requires caution.

Diazepam in the exchange application does not affect the pharmacokinetics of paroxetine.

Paroxetine significantly increases the concentration in plasma protsiklidina, Therefore, the appearance of anticholinergic side effects should be reduced dose protsiklidina.

In clinical trials of paroxetine did not affect the level of propranolol in the blood.

In some cases, the observed increase in the concentration of theophylline in blood. Despite, that in the course of clinical studies, the interaction between paroxetine and theophylline is not proven, recommended regular monitoring of theophylline in the blood.

Strengthening the action of ethanol while the use of paroxetine is not revealed. However, due to the effect of paroxetine on the enzyme system of liver exclusion must be drinking during treatment with paroxetine.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at temperature from 15 ° to 30 ° C. Shelf life – 5 years.