Rexetine, 20 mg 30 pcs

Rexetine has antidepressant effects.

Pharmacodynamics

Inhibits in the central nervous system neuronal reuptake of serotonin. Has little effect on the neuronal takeover of norepinephrine and dopamine. It also has anxiolytic and psychostimulant properties.

Pharmacokinetics

Paroxetine is well absorbed after oral administration. It is metabolized mainly in the liver, with the formation of mostly inactive metabolites. Simultaneous intake of food does not affect the absorption and pharmacokinetics of paroxetine. Paroxetine binds 93-95% to plasma proteins.

The half-life of paroxetine ranges from 6 to 71 hours, but averages one day.

Dynamic equilibrium in blood plasma is reached 7-14 days after initiation of therapy; thereafter, pharmacokinetics does not change during long-term therapy. Approximately 64% of paroxetine is excreted in the urine (2% unchanged, 62% as metabolites); about 36% is excreted through the gastrointestinal tract mainly as metabolites, less than 1% is excreted unchanged in the feces.
Plasma concentrations of paroxetine increase with hepatic and renal dysfunction, as well as in old age.

Indications

Active ingredient

Composition

1 coated tablet contains:

Active substance:

Paroxetine hydrochloride hemic hydrate 22.76 mg, which corresponds to the content of paroxetine 20 mg.

Auxiliary substances:

Hypromellose, 15 mg;

Calcium hydrophosphate dihydrate, 244.24 mg;

Sodium carboxymethyl starch – 15 mg;

Magnesium stearate – 3 mg

Shell film:

Hypromellose – 7.2 mg;

Macrogol 400 – 0.07 mg;

p> macrogol 6000 – 0.956 mg;

polysorbate 80 – 0.044 mg;

titanium dioxide – 1.03 mg.

How to take, the dosage

Overly, once daily, preferably in the morning, with a meal, without chewing.

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

For depression: the recommended daily dose is 20 mg. As with other antidepressants, the effect in most cases develops gradually. In some patients it may be necessary to increase the dose of the drug. Depending on the patient’s response to therapy, the daily dose may be increased by 10 mg at 1 week intervals until a therapeutic effect is achieved; the maximum daily dose is 50 mg.

In obsessive-compulsive disorders (obsessive compulsive disorder): the initial dose is 20 mg/day. The dose may be increased by 10 mg weekly, until the desired therapeutic response is achieved. The maximum daily dose is usually 40 mg, but should not exceed 60 mg.

In panic disorder: the recommended therapeutic dose is 40 mg/day. Therapy should begin with a small (10 mg/day) dose, with weekly increases of 10 mg/day, until the desired effect is achieved. The maximum daily dose should not exceed 60 mg. The recommended low starting dose of the drug is due to the possibility of a temporary increase in the intensity of symptoms at the beginning of therapy.

In case of sociophobia: therapy can be started with a dose of 20 mg/day. If after 2-week course of the therapy no essential improvement in a patient’s condition is observed, the dose of the preparation can be increased weekly by 10 mg until the desired effect is achieved. The maximum daily dose should not exceed 50 mg. For maintenance therapy, a daily dose of 20 mg is usually sufficient.

In generalized anxiety disorder: the recommended therapeutic dose is 20 mg/day. Depending on the patient’s response to therapy, the daily dose may be increased gradually by 10 mg; the maximum daily dose is 50 mg.

In post-traumatic stress disorder: the recommended therapeutic dose is 20 mg/day. Depending on the patient’s response to therapy, the daily dose may be increased intermittently by 10 mg, the maximum daily dose being 50 mg.

Depending on the clinical condition of the patient, maintenance therapy is necessary to prevent possible relapses. This course after the disappearance of depression symptoms may be 4-6 months, and with obsessive and panic disorders even more. As with other psychotropic drugs, abrupt discontinuation of treatment should be avoided. Serum levels may increase above normal in frail and elderly patients, so 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 should not exceed 40 mg/day.

The drug is not indicated in children because of lack of clinical experience.

In patients with renal (creatinine Cl

Interaction

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

Like other serotonin reuptake inhibitors, an undesirable interaction between MAOI inhibitors and paroxetine has been observed in animal experiments.

The concomitant use of paroxetine with tryptophan leads to headache, nausea, increased sweating, and dizziness, so this combination should be avoided.

A pharmacodynamic interaction has been suggested between paroxetine and warfarin (increased bleeding has been noted with unchanged prothrombin time); use of this combination requires caution.

In concomitant use of paroxetine with sumatriptan, general weakness, hyperreflexia, and coordination disorders have been noted. If their concomitant use is necessary, special caution should be exercised (medical monitoring is required).

When used concomitantly, paroxetine may inhibit the metabolism of tricyclic antidepressants (due to inhibition of CYP2D6 isoenzyme), therefore, the use of such combination requires caution and dose reduction of tricyclic antidepressants.

Drugs that increase or inhibit the activity of liver enzyme systems may affect the metabolism and pharmacokinetics of paroxetine. When concomitant use with inhibitors of liver metabolic enzymes, the lowest effective dose of paroxetine should be used. Co-administration with liver enzyme inducers does not require adjustment of the initial dose of paroxetine; further dosage changes depend on the clinical effect (efficacy and tolerability).

Paroxetine significantly inhibits the activity of CYP2D6 isoenzyme. Therefore, concomitant use of paroxetine with agents metabolized with the participation of this isoenzyme, including With some antidepressants (e.g. nortriptyline, amitriptyline, imipramine, desipramine and fluoxetine), phenothiazines (e.g. thioridazine), class 1 C antiarrhythmic drugs (e.g. propafenone, flecainide and encainide) or with those drugs that block its activity (e.g. quinidine, cimetidine, codeine).

There are no reliable clinical data about inhibition of CYP3A4 isoenzyme by paroxetine; therefore, it is possible to use with the drugs which inhibit this enzyme (e.g., terfenadine).

Cimetidine inhibits some cytochrome P450 isoenzymes. Consequently, when paroxetine is coadministered with cimetidine, plasma levels of paroxetine at the equilibrium state are increased.

Phenobarbital increases the activity of certain cytochrome P450 isoenzymes. Concomitant use of paroxetine with phenobarbital decreases the plasma concentration of paroxetine and shortens its T1/2.

When paroxetine and phenytoin are used together, plasma concentrations of paroxetine are decreased and the incidence of phenytoin side effects may increase. When using other anticonvulsants, the frequency of their side effects may also increase. In patients with epilepsy treated with long-term carbamazepine, phenytoin or sodium valproate, additional administration of paroxetine did not cause changes in pharmacokinetic and pharmacodynamic properties of anticonvulsants; no increase in paroxysmal seizure activity was observed.

Paroxetine binds significantly to plasma proteins. When concomitant use with drugs, which also bind with plasma proteins, against the background of increased concentration of paroxetine in blood plasma, an increase in side effects is possible.

Because of the lack of sufficient clinical experience of concomitant use of digoxin with paroxetine, the prescription of this combination requires caution.

Diazepam has no effect on the pharmacokinetics of paroxetine when administered as a regimen.

Paroxetine significantly increases the plasma concentration of procyclidine; therefore, if anticholinergic side effects occur, the procyclidine dose must be decreased.

In clinical trials, paroxetine did not affect propranololol blood levels.

In some cases, an increase in theophylline blood concentrations was noted. Although no interaction between paroxetine and theophylline has been proven in clinical studies, regular monitoring of theophylline blood levels is recommended.

An increase in the effect of ethanol when used concomitantly with paroxetine has not been found. However, due to the effect of paroxetine on liver enzyme system, it is necessary to avoid drinking alcohol during treatment with paroxetine.

Special Instructions

Paroxetine is contraindicated concomitantly with MAO inhibitors and for 14 days after their withdrawal. Subsequently, paroxetine should be used with extreme caution, starting treatment with low doses and gradually increasing doses until the desired therapeutic effect is achieved. No treatment with MAO inhibitors should be started within 14 days after ending paroxetine therapy.

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

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

Because of the predisposition to suicide attempts in depressed patients and patients with drug addiction during withdrawal, this category of patients should be closely monitored during treatment.

In many cases, hyponatremia has been noted, especially in elderly patients who receive diuretics. After withdrawal of paroxetine, blood sodium levels normalize.

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

Hyperglycemic conditions have rarely been reported during paroxetine use.

Suicidal/Suicidal Thinking

Depression is associated with an increased risk of suicidal ideation, autoaggression, and suicide. This risk persists until remission occurs. Because improvement may not occur within the first few weeks or more of initiating treatment, patients should be closely monitored until such improvement occurs. Current clinical experience suggests that with antidepressant treatment, the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Rexetine is prescribed may also be combined with an increased risk of suicidal behavior. In addition, these conditions may be concomitant with major depressive disorder. The same precautions that are taken when treating patients with major depressive disorder should be followed when treating patients with other psychiatric disorders. Patients with a history of suicidal behavior or thoughts, or who demonstrate a significant degree of suicidal ideation prior to treatment, are at greater risk for suicidal thoughts or suicide attempts, and should be closely monitored during treatment. These patients have an increased risk of suicide in the 18-29 age range, so treatment with the drug should be carefully monitored.

Patients (and those assisting patients) should be prepared to monitor for emergencies – the appearance of suicidal intentions/behavior or thoughts of autoaggression, in order to seek medical attention immediately if these symptoms are present.

Effects on driving and operating ability

Controlled studies have shown no adverse effects of paroxetine on psychomotor or cognitive function. Despite this, at the beginning of therapy, for a period individually determined, it is not permissible to drive a vehicle or work in hazardous conditions requiring rapid reaction. The degree of restriction is determined on an individual basis.

Contraindications

Side effects

Gastrointestinal tract, liver: Nausea (12%); sometimes constipation, diarrhea, decreased appetite. Rarely, increased liver function tests; sometimes severe impairment of liver function. There is no proven causal relationship between paroxetine intake and changes in liver enzyme activity, but in case of liver dysfunction it is recommended to stop using paroxetine.

CNS disorders: somnolence (9%); tremor (8%); general weakness and increased fatigability (7%); insomnia (6%); in some cases headache, increased irritability, paresthesia, dizziness, somnambulism. Rarely, extrapyramidal disorders and oro-facial dystonia were observed. Extrapyramidal disorders were observed mainly with previous intensive use of neuroleptics. Rarely, epileptiform seizures have been observed, which is also characteristic of therapy with other antidepressants; increased intracranial pressure.

Autonomic nervous system disorders: increased sweating (9 %), dry mouth (7 %).

Senses: In some cases vision disorders and mydriasis were noted; rarely – an attack of acute glaucoma.

Cardiovascular system: In single cases tachycardia, ECG changes, blood pressure fluctuations, fainting have been described.

Anxiety of the sexual sphere and urinary system: Disorders of ejaculation (13%), in some cases, changes in libido, rarely difficulty in urination.

Electrolyte balance disorder: In single cases hyponatremia with the development of peripheral edema, impaired consciousness or epileptiform symptoms were noted. After drug withdrawal the sodium level in blood normalizes. In some cases this condition has developed due to hyperproduction of antidiuretic hormone. Most such cases were observed in elderly patients who were receiving diuretics and other drugs in addition to paroxetine.

Dermatological and hypersensitivity reactions: Skin hyperemia, subcutaneous hemorrhages, edema in the face and extremities, anaphylactic reactions (urticaria, bronchospasm, angioedema), skin itching have been described in rare cases.

Other: In single cases myopathies, myalgias, hyperglycemia, rarely hyperprolactinemia, galactorrhea, hypoglycemia, fever and influenza-like condition development were noted. Rarely, thrombocytopenia develops, but a causal relationship with the drug intake has not been proven. Paroxetine administration may be accompanied by an increase or decrease in body weight. Several cases of increased bleeding have been described (See Warnings). Paroxetine, compared to tricyclic antidepressants, is less likely to cause dry mouth, constipation, and drowsiness. Abrupt withdrawal may cause dizziness, sensory disturbances (e.g., paraesthesias), anxiety, sleep disturbances, agitation, tremors, nausea, increased sweating, and confusion, so discontinuing the drug should be done gradually, it is reasonable to reduce doses every other day.

Overdose

Symptoms: nausea, vomiting, tremor, dilated pupils, dry mouth, general agitation, increased sweating, drowsiness, dizziness, facial hyperemia. No coma or seizures were observed. Fatal outcome has rarely been observed, usually with simultaneous overdose of paroxetine and another drug causing adverse interactions. Signs of overdose occur when 2 g of paroxetine is used at one time or when a large dose of paroxetine is taken with other drugs or with alcohol. Paroxetine therapy is safe in a large dose range.

Treatment: gastric lavage, 20-30 g of activated charcoal every 4-6 h for the first 24-48 h; the airway should be cleared, oxygenation if necessary. Monitoring of vital body functions and general measures aimed at their maintenance are carried out. There is no specific antidote. Forced diuresis, hemodialysis or hemoperfusion are ineffective if a large dose of paroxetine has entered the tissues from the blood.

Pregnancy use

The safety of paroxetine use in pregnancy has not been studied, therefore, it should not be used during pregnancy and lactation, unless, from the medical point of view, the potential benefit of treatment exceeds the possible risk associated with taking the drug.

If it is necessary to use the drug during lactation, discontinuation of breastfeeding should be considered.

Women of childbearing age should avoid conception while using the drug (use reliable contraception methods).

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