Reksetin

General characteristics. Structure:

One tablet, coated, Reksetina of 20 mg contains 20 mg of a paroksetin (in the form of 22,760 mg of a paroksetin of a hydrochloride of a gemigidrat).
One tablet, coated, Reksetina of 30 mg contains 30 mg of a paroksetin (in the form of 34,140 mg of a paroksetin of a hydrochloride of a gemigidrat).

Excipients for tablets, coated, 20 mg: calcium hydrophosphate dihydrate, starch sodium glycollate (type A), gipromelloz, magnesium stearate, macrogoal 400, 6000, polysorbate 80, titanium dioxide of Tsv. Index: 77891, E 171.
Excipients for tablets, coated, 30 mg: calcium hydrophosphate dihydrate, starch sodium glycollate (type A), gipromelloz, magnesium stearate, macrogoal 400, 6000, polysorbate 80, titanium dioxide of Tsv. Index: 77891, E 171.

Pharmacological properties:

Pharmacodynamics. Inhibits the return neyronalny serotonin reuptake in the central nervous system. Influences neyronalny capture of noradrenaline and dopamine a little. Has also anxiolytic and psychogogic property.

Pharmacokinetics. After oral administration пароксетин it is well soaked up. It is metabolized generally in a liver, with education, preferential, inactive metabolites. The concomitant use of food does not influence absorption and pharmacokinetics of a paroksetin. Paroksetin contacts proteins of a blood plasma for 93-95%.
The elimination half-life of a paroksetin is ranging from 6 till 71 o'clock, but averages one days.
The dynamic equilibrium in a blood plasma is reached in 7-14 days after the beginning of therapy, further the pharmacokinetics at long therapy does not change. About 64% of a paroksetin are removed with urine (2% in not changed look, 62% in the form of metabolites); about 36% are allocated through digestive tract generally in the form of metabolites, less than 1% are allocated with a stake in not changed look.
Concentration of a paroksetin in a blood plasma increases at an abnormal liver function and kidneys, and also in advanced age.

Indications to use:

To apply strictly on doctor's orders in order to avoid complications!

- A depression of various etiology, including the states which are followed by alarm;
- Obsessivno-kompulsivnye frustration (obsessional syndrome);
- Panic frustration, including with fear of stay in crowd (agoraphobia);
- Sociophobia;
- Generalized Alarming Frustration (GAF);
- Posttraumatic stressorny frustration.
- It is applied also within antirecurrent treatment.

Route of administration and doses:

- Reksetin it is necessary to accept once a day, it is desirable in the morning, during food, without chewing.
As well as at therapy by other antidepressants, depending on a clinical condition of the patient in two-three weeks the dosage of drug can be changed.
At depressions the recommended daily dose makes 20 mg.

- As well as at use of other antidepressants, the effect in most cases develops gradually. At some patients increase in a dose of drug can be required. Depending on reaction of the patient to therapy, the daily dose can be increased by 10 mg at an interval of one week, before achievement of therapeutic effect; the maximum daily dose makes 50 mg.
At obsessivno-kompuljsivny frustration (obsessional syndrome) the initial dose makes 20 mg a day. The dose can be increased by 10 mg weekly, before achievement of the necessary therapeutic answer. The maximum daily dose makes, as a rule, 40 mg, but should not exceed 60 mg.
At panic frustration the recommended therapeutic dose makes 40 mg a day. Therapy should be begun with small (10 mg a day) doses, with weekly increase in dosages on 10 mg a day before achievement of required effect. The maximum daily dose should not exceed 60 mg. The recommended low initial dose of drug is caused by a possibility of temporary increase of intensity of symptoms of a disease at the beginning of therapy.
At sotsiofobiya therapy it is possible to begin with a dose 20 mg a day. If after a two-week course of treatment significant improvement in a condition of the patient is not noted, the dose of drug can be raised weekly on 10 mg to achievement of desirable effect. The maximum daily dose should not exceed 50 mg. The daily dose of 20 mg is usually sufficient for a maintenance therapy.
At generalized alarming frustration: The recommended therapeutic dose makes 20 mg a day. Depending on reaction of the patient to therapy, the daily dose can be increased gradually on 10 mg; the maximum daily dose makes 50 mg.
At posttraumatic stressful frustration: The recommended therapeutic dose makes 20 mg a day. Depending on reaction of the patient to therapy, the daily dose can be increased periodically on 10 mg, the maximum daily dose makes 50 mg.

- Depending on a clinical condition of the patient, for prevention of a possibility of a recurrence it is necessary to carry out a maintenance therapy. This course after disappearance of symptoms of a depression can make 4-6 months, and at obsessivny and panic frustration and more. As well as at use of other psychotropic drugs, it is necessary to avoid the sudden termination of a course of treatment. (See: Side effects)
At the weakened and elderly patients drug level in blood serum therefore the recommended initial dose makes 10 mg a day can increase above usual. This dose can be increased by 10 mg weekly, depending on a condition of the patient.
The maximum dose should not exceed 40 mg a day.
Drug is not shown to children due to the lack of clinical experience.
At renal (clearance of creatinine <30 ml a minute) or a liver failure concentration of a paroksetin increases in a blood plasma therefore the recommended daily dose of drug in these cases makes 20 mg. This dose can be increased depending on a condition of the patient, but it is necessary to aim to support a dose at minimum possible level.

Features of use:

1. Reception of a paroksetin along with MAO inhibitors and within two weeks after their cancellation is contraindicated. Further, пароксетин it is necessary to apply with extra care, beginning a course of treatment with small doses and gradually raising dosages to achievement of desired therapeutic effect. After the end of therapy paroksetiny within two weeks it is impossible to begin a course of treatment with MAO inhibitors.
2. Existence of a maniacal state in the anamnesis: As well as at reception of other antidepressants if the patient was in a maniacal state earlier, during reception of a paroksetin, it is necessary to consider a possibility of approach of a recurrence.
3. Cardiovascular system: At the broken function of cardiovascular system drug should be used with care.
4. Epilepsy: As well as other antidepressants, пароксетин it is necessary to apply with care in the presence of epilepsy in the anamnesis. On clinical observations, пароксетин causes epileptiform attacks in 0,1% of patients. It is necessary to interrupt a course of treatment of patients at whom similar frustration were shown!
5. Electroconvulsive therapy (EST): There is no sufficient experience of simultaneous use of EST and therapy paroksetiny.
6. Due to the predisposition to suicidal attempts at patients with a depression and patients with drug addiction in abstinence, in the course of treatment of this category of patients careful observation is necessary.
7. Hyponatremia: In many cases the hyponatremia, especially at elderly patients who receive diuretics was noted. After cancellation of a paroksetin sodium level in blood is normalized.
8. The raised bleeding: In certain cases against the background of treatment paroksetiny there was bleeding (generally an ecchymoma and a purpura).
9. Glaucoma: As well as other selective serotonin reuptake inhibitors (SSRI), пароксетин the mydriasis causes therefore in the presence of glaucoma to apply with care.
10. Hyper glycemic states were seldom noted during acceptance of a paroksetin.

Preventions:
During therapy paroksetiny contraception is recommended to women of childbearing age.

Driving:
The controlled researches did not reveal negative effect of a paroksetin on psychomotor or cognitive function. Despite it, at the beginning of a therapy course, during individually established period, it is impossible to drive the car or to work in the conditions of the increased danger, demanding speed of reaction. Extent of restriction is defined individually.

Side effects:

Frequency of manifestation and intensity of side effects in the course of therapy decreases therefore at their development continuation of administration of drug is in most cases possible. By-effects on bodies and systems (as a percentage the revealed ratio from total quantity of the patients receiving this treatment);
- From a GIT, a liver: Nausea (12%); sometimes lock, diarrhea, loss of appetite. Increase in hepatic functional trials is rare; sometimes heavy abnormal liver function. Between reception of a paroksetin and change of activity of enzymes of a liver relationship of cause and effect is not proved, but in case of an abnormal liver function phase-out of a paroksetin is recommended.
- From TsNS: Drowsiness (9%); tremor (8%); general weakness and increased fatigue (7%); sleeplessness (6%); in some cases headache, acrimony, paresthesias, dizziness, noctambulation. Extrapyramidal disturbances and oro-facial dystonia were seldom observed. Extrapyramidal frustration are noted preferential at the previous intensive use of neuroleptics. Epileptiform attacks were seldom observed that is peculiar also to therapy by other antidepressants; increase in intracranial pressure.
- From the autonomic nervous system: The increased sweating (9%), dryness in a mouth (7%).
- From sense bodys: The vision disorder, a mydriasis are in some cases noted; seldom - an attack of acute glaucoma.
- From cardiovascular system: Tachycardia, changes of an ECG, lability of arterial pressure, unconscious states are in some cases described.
- From the sexual sphere and an urinary system: Frustration of an ejaculation (13%), in some cases change of a libido, is rare difficulty of an urination.
- Disturbance of electrolytic balance: The hyponatremia with development of peripheral hypostases, disturbance of consciousness or epileptiform symptomatology is in some cases noted. After drug withdrawal sodium level in blood is normalized. In certain cases this state developed owing to hyperproduction of antidiuretic hormone. The majority of similar cases was observed at aged patients who in addition to a paroksetin received diuretic and other drugs.
- Dermatological reactions and hypersensitivity reactions: The dermahemia, hypodermic hemorrhages, hypostases in a face and extremities, anaphylactic reactions (a small tortoiseshell, a bronchospasm, a Quincke's disease), a skin itch are in rare instances described.
- Others: In isolated cases myopathies, mialgiya, a hyperglycemia, seldom a giperprolaktinemiya, a galactorrhoea, a hypoglycemia, temperature increase and development of a grippo-like state were noted. Seldom thrombocytopenia develops, but relationship of cause and effect with administration of drug is not proved. Reception of a paroksetin can be followed by increase or decrease in body weight. Several cases of the raised bleeding are described (See Preventions). Paroksetin, in comparison with tricyclic antidepressants, causes dryness in a mouth, a lock and drowsiness less often. Sudden drug withdrawal can cause dizziness, sensitivity disturbances (for example, paresthesias), sensation of fear, a sleep disorder, agitation, a tremor, nausea, the increased sweating and confusion of consciousness therefore the therapy termination by drug needs to be made gradually, reasonablly to reduce dosages every second day.

Interaction with other medicines:

Food, antacids: Food and antiacid drugs do not influence absorption and pharmacokinetics of a paroksetin.

MAO inhibitors: Like other inhibitors of the return serotonin reuptake, in animal experiments undesirable interaction between MAO inhibitors and paroksetiny was noted (See: Special instructions).

Tryptophane: At patients at simultaneous use of tryptophane and a paroksetin the headache, nausea, the increased sweating and dizziness therefore it is necessary to avoid combined use of a paroksetin and tryptophane were noted.

Warfarin: Between paroksetiny and warfarin pharmakodinamichesky interaction (at not changed prothrombin time the raised bleeding is noted) is supposed. Therefore пароксетин it is necessary to appoint with extra care the patient accepting peroral anticoagulants.

Sumatriptan: In not numerous cases of combined use the general weakness, a hyperreflexia, lacks of coordination were noted. In need of simultaneous use of a sumatriptan and inhibitor of the return serotonin reuptake, the last needs to be carried out under strict medical control.

Benzodiazepines (oxazepam), barbiturates, neuroleptics: At combined use of a paroksetin and the specified means of data on strengthening of sedation (drowsiness) inherent to them it is noted. There is not enough experience about combined use of a paroksetin with neuroleptics therefore in these cases it is necessary to use drug with care (See: By-effects: extrapyramidal disturbances).

Tricyclic antidepressants (TTsA): As well as at combined use of other inhibitors of the return serotonin reuptake with drugs TTsA, care as it пароксетин can slow down the metabolism of TTsA which is carried out with participation of an isoenzyme (CYP) IID6 is necessary. Therefore the dose of TTsA needs to be lowered. (See: Combined use with the drugs inducing and inhibiting metabolic fermental system)
Lithium: Sufficient experience of combined use of lithium with paroksetiny or with other inhibitors of the return serotonin reuptake is not saved up yet therefore it is necessary to apply with care, under regular control of level of lithium in blood.

Combined use with the drugs inducing and inhibiting metabolic fermental system:
Drugs which strengthen or brake activity of fermenty systems of a liver, can influence metabolism and pharmacokinetics of a paroksetin. At combined use with inhibitors of metabolic enzymes of a liver it is necessary to use the smallest effective dose of a paroksetin. Combined use with inductors of liver enzymes does not demand correction of an initial dose of a paroksetin; further change of dosages depends on clinical effect (efficiency and portability). Drugs which metabolism is carried out with the participation of CYP 2D6 isoenzyme. Paroksetin authentically brakes activity of this enzyme. Therefore extra care is demanded by its simultaneous use with drugs which metabolism happens with the participation of this isoenzyme, including: some antidepressants (for example, нортриптилин, amitriptyline, Imipraminum, desipramine and fluoxetine), fenotiazina (for example, thioridazine), antiarrhytmic drugs of group 1C (for example, пропафенон, флекаинид and энкаинид) or which block its action (for example, quinidine, Cimetidinum, codeine).

Drugs which metabolism is carried out with the participation of CYP 3A4 isoenzyme: There are no reliable clinical data about inhibition paroksetiny an isoenzyme of CYP 3A4 therefore with the drugs inhibiting this enzyme (for example, терфенадин) it is possibly possible to apply without problems.

Cimetidinum: Cimetidinum inhibits some isoenzymes of P450 cytochrome. Thereof, at combined use the level of concentration of a paroksetin in a blood plasma at a stage of a dynamic equilibrium increases.

Phenobarbital: Phenobarbital increases activity of some isoenzymes of P450 cytochrome. At combined use concentration of a paroksetin in a blood plasma decreases, and also the elimination half-life is shortened.

Anticonvulsant drugs (Phenytoinum): At combined use of a paroksetin and Phenytoinum concentration of a paroksetin in a blood plasma decreases, however increase in frequency of side effects of Phenytoinum is possible. At use of other anticonvulsant drugs the frequency of their side effects can also increase. At patients with epilepsy, treated a long time carbamazepine, Phenytoinum or Valproatum of sodium, additional purpose of a paroksetin did not cause changes in pharmacokinetic and pharmakodinamichesky properties of anticonvulsant drugs; increase in paroxysmal convulsive readiness was not noted.

The medicines contacting proteins of plasma:
Paroksetin substantially contacts proteins of a blood plasma. At simultaneous use with drugs which also contact proteins of plasma against the background of increase in concentration of a paroksetin in a blood plasma strengthening of side effects is possible.

Digoxin: As sufficient clinical experience about combined use is not available, recommended care at their simultaneous use.

Diazepam: Diazepam at course use does not influence pharmacokinetics of a paroksetin.

Protsiklidin: Paroksetin authentically increases concentration of a protsiklidin in a blood plasma therefore at emergence of anticholinergic side effects it is necessary to lower a dose of a protsiklidin.

Beta adrenoblockers: In clinical tests пароксетин did not influence propranolol level in blood.

Theophylline: Increase in concentration of theophylline in blood is in certain cases noted. In spite of the fact that in the course clinical trials interaction between paroksetiny and theophylline is not proved, regular control of level of theophylline in blood is recommended.

Alcohol: Strengthening of effect of alcohol at simultaneous use with paroksetiny is not revealed. However owing to influence of a paroksetin on fermental system of a liver the exception of the use of alcoholic drinks is necessary during treatment paroksetiny.

Contraindications:

- Hypersensitivity to drug components in the anamnesis.
- Therapy by inhibitors of a monoamino-oxidase (MAO) and the period after the treatment termination by MAO inhibitors within two weeks.
- Pregnancy and period of a lactation. Safety of use of a paroksetin at pregnancy is not studied therefore it should not be applied at pregnancy and in the period of a lactation, except for cases when from the medical point of view the potential advantage of treatment surpasses the possible risk connected with administration of drug.
- Children's age up to 18 years (due to the lack of clinical experience).

Overdose:

Therapy paroksetiny is safe in the big range of doses. Signs of overdose were shown at single-step use of 2000 mg of a paroksetin, or at reception of a high dose of a paroksetin with other drugs, or with alcohol. Overdose signs: nausea, vomiting, a tremor, expansion of pupils, dryness in a mouth, the general excitement, the increased sweating, drowsiness, dizziness, erubescence of the person. Coma or spasms were not noted. The fatal outcome at the same time was noted seldom, usually at the simultaneous overdose of a paroksetin and other drug causing adverse interactions. There is no specific antidote.

At overdose it is necessary to provide release of respiratory tracts, if necessary an oksigenization, a gastric lavage or calling of vomiting, giving 20-30 g of absorbent carbon each 4-6 hours during the first 24-48 hours. Constant control cordial and other vital functions is recommended. The artificial diuresis, a hemodialysis or hemoperfusion are a little effective if the high dose of a paroksetin came from blood to fabrics.

Storage conditions:

To store at a temperature of 15-30 °C, in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

20 mg of a paroksetin (in the form of a paroksetin of a hydrochloride of a gemigidrat) in each tablet, coated. On 30 tablets, coated, in packaging. 30 mg of a paroksetin (in the form of a paroksetin of a hydrochloride of a gemigidrat) in each tablet, coated. On 30 tablets, coated, in packaging. 10 tablets in the blister, 3 blisters place in a pack cardboard.