Paraxinum

General characteristics. Structure:

Active ingredient: a paroksetina of a hydrochloride of hemihydrate in terms of пароксетин 20 mg;

Excipients: hydrophosphate calcium a dihydrate, sodium krakhmalglikolit, type A, cellulose microcrystallic, magnesium stearate, a covering for drawing a cover of Opadry II White (polyethyleneglycol, polyvinyl alcohol, talc, titanium E 171 dioxide).

Pharmacological properties:

Pharmacodynamics. Paroksetin is strong selection inhibitor of absorption by neurons of a brain of a 5-gidroksitriptamin (5-HT, serotonin) that causes its antidepressive action and efficiency.
On chemical structure пароксетин does not treat other selective serotonin reuptake inhibitors or antidepressants tricyclic, tetracyclic or any others known now.
Antidepressive effect of drug is shown approximately in 10 days of system reception. Against the background of treatment reduction of a condition of alarm, a depression and frustration of a dream is observed.

Pharmacokinetics. After oral administration пароксетин it is well absorbed in digestive tract; its bioavailability fluctuates within 50-100%. Presence of food, milk or antiacid funds for absorption does not influence. The maximum concentration in plasma is reached within 2-8 hours after intake. Paroksetin is actively metabolized at primary passing through a liver. The elimination half-life at adults averages 24 hours. The elimination half-life is extended at patients with heavy abnormal liver functions or kidneys. Removal of metabolites two-phase: in the beginning as a result of the first passing through a liver, then as a result of system removal. About 64% of a dose of a metabolizirovanny paroksetin are removed with urine; about 2% - in not changed look. About 36% of a dose are removed with a fecal masses (the maintenance of not changed paroksetin - less than 1%). Stable system levels of a paroksetin in blood are reached for 7-14 days later began therapies, during the long period of treatment the pharmacokinetics practically does not change.
Linkng with proteins of plasma makes 95%.
Nonlinear dependence of pharmacokinetic parameters on a drug dose which is shown at increase in a dose and/or duration of treatment is noted.

Indications to use:

- Depression. Treatment of a depression of any type, including a situational and heavy depression, including the depression which is followed by alarm. In case of the satisfactory response to treatment continuation of therapy is effective for prevention of a recurrence of a depression.
- Obsessivno-kompulsivnoye frustration. Treatment and prevention of a recurrence of obsessivno-compulsive frustration.
- Panic frustration. Treatment and prevention of a recurrence of panic frustration with the accompanying agoraphobia or without it.
- Social phobias / социально-тревожные frustration. Treatment of social phobias / social and alarming states.
- Generalized alarming frustration. Treatment and prevention of a recurrence of generalized alarming frustration.
- Posttraumatic stressful frustration. Treatment of posttraumatic stressful frustration.

Route of administration and doses:

General recommendations.

Paraxinum is applied orally, it is recommended to accept once a day, in the morning, during food. It is necessary to swallow of a tablet without chewing.
As well as for all other antidepressive means, the dose needs to be selected carefully individually for the first 2-3 weeks of treatment, and then to adjust it depending on clinical manifestations.
The course of treatment has to be quite long, sufficient to provide elimination of symptoms. As well as at use of other means for treatment of mental disorders, it is necessary to avoid sudden drug withdrawal.

Depression. The recommended dose - 20 mg a day. If this dose is inefficient, for improvement fortunes a dose are increased on 10 mg a day to the maximum dose 50 mg a day. It is possible to select a dose 2-3 weeks from the moment of the beginning of therapy. For treatment of acute episodes of a depression duration of treatment has to make several months and more.

Obsessivno-kompulsivnoye frustration. The recommended dose - 40 mg a day. Treatment it is necessary to begin 20 mg with a dose and to gradually increase a dosage by 10 mg weekly. If necessary a dose it is possible to increase 60 mg to the maximum dose.

Panic frustration. The recommended dose makes 40 mg a day. Therapy it is necessary to begin with a dose 10 mg a day, increasing it weekly by 10 mg. For achievement of the corresponding therapeutic effect Paroksin's dose can be increased to the maximum dose making 60 mg a day.

Social and alarming frustration / social phobias. The recommended dose - 20 mg a day. For some patients the dose can be increased gradually by 10 mg a day - depending on clinical effect of treatment, up to 50 mg a day. The interval between increase in doses has to be not less than 1 week.

Generalized alarming frustration. The recommended dose - 20 mg a day. For some patients with insufficient efficiency at reception of 20 mg it is possible to increase a dose gradually by 10 mg a day, depending on clinical effect, to 50 mg a day.

Posttraumatic stressful frustration. The recommended dose - 20 mg a day. For some patients with insufficient efficiency at reception of 20 mg it is possible to increase a dose gradually by 10 mg a day, depending on clinical effect, to 50 mg a day.

Patients of advanced age. Treatment is begun with use of a usual initial dose for adults which then it is possible to increase gradually to 40 mg a day.

Paroksin's cancellation.
As well as at use of other drugs for treatment of mental diseases, it is necessary to avoid sudden drug withdrawal. Use of the mode of gradual reduction of a dose of drug is possible that includes reduction of a daily dose by 10 mg a day at an interval of one week. After achievement of the mode of dosing of 20 mg a day patients accept a week more drug in such dose before its full cancellation. In case of strongly expressed symptoms during reduction of a dose or after cancellation of treatment it is necessary to resolve an issue of resuming of treatment in the previous dose. It is possible to continue to reduce a dose later, but at slower speed.

Features of use:

Use during pregnancy and feeding by a breast.
Pregnancy.
The teratogenic or embriotoksichesky effect of a paroksetin in researches on animals is not revealed.
According to recent epidemiological researches of observation of results of pregnancy at the women treated by antidepressants in І a pregnancy trimester it was reported about increase in risk of inborn disturbances of development, mainly cardiovascular (for example, defect of an interatrial or interventricular partition), connected with reception of a paroksetin. According to these data it is possible to assume that the risk of the birth of babies with cardiovascular defect at the women treated paroksetiny during pregnancy makes about 1 on 50 in comparison with the expected risk of emergence of such defect in the general population, a component about 1 on 100.

The doctor has to consider a possibility of use of alternative treatment of the pregnant woman or the woman planning pregnancy and to appoint пароксетин only when the expected advantage for mother exceeds potential risk for a fruit.

It is necessary to conduct examination of newborns if the pregnant woman continued to accept Paroksin in ІІІ a pregnancy trimester as there are messages on development of complications in newborns at treatment of mother paroksetiny or other selective serotonin reuptake inhibitors during this period though the cause and effect interrelation with administration of drug is not established. It was reported about such effects: a respiratory distress, cyanosis, an apnoea, spasms, fluctuation of temperature, difficulty when feeding, vomiting, a hypoglycemia, arterial hypertension, hypotension, a hyperreflexia, a tremor, excitability, block, constant crying and drowsiness. Sometimes these symptoms connect with drug withdrawal. In most cases they arise at once or soon (<24 hours) after the delivery.

According to epidemiological researches, use of selective serotonin reuptake inhibitors (including пароксетин) at pregnant women, especially on late durations of gestation, was associated with the increased risk of development of persistent pulmonary hypertensia in newborns. At the women applying inhibitors of the return serotonin reuptake on late durations of gestation, such risk increased by 4-5 times compared with the general group of patients.

Feeding by a breast.
A small amount of a paroksetin is excreted in breast milk. No signs of influence of drug on newborns were revealed, however Paroksin it is not necessary to apply during feeding by a breast, except cases when the expected advantage for mother exceeds possible risk for the child.

Children.
Paraxinum is not shown for treatment of children and teenagers aged up to 18 years. By results of controlled clinical trials it was not shown to efficiency and confirmatory data concerning use of a paroksetin for treatment of the children sick with a depression are not obtained.

It is necessary to appoint Paraxinum with care the patient having episodes of a mania and attacks in the anamnesis. Before an initiation of treatment antidepressants of patients it is necessary to inspect carefully for the purpose of identification at them any risk of developing of bipolar disorder. Such inspection has to include detailed studying of a case history of the patient, including existence of suicide attempts, bipolar disorders and a depression at family members. It is necessary to consider that Paroksin do not apply to treatment of bipolar disorder.

Deterioration in a clinical state and risk of a suicide.
The patients of young age especially sick with heavy depressive frustration, can have the increased risk of suicide behavior during treatment by Paroksin.

At patients with depressive frustration symptoms of a depression can become aggravated and/or form suicide thoughts and behavior irrespective of, they accept antidepressants or not. This risk remains until there occurs essential remission. The risk of suicides can increase at early stages of recovery.

Patients with suicide behavior and intentions in the past, young patients and patients with constant suicide mood by the beginning of a course of treatment, are group of the increased risk concerning attempts of suicide and suicide thoughts. For identification of deterioration in a clinical state (including development of new symptoms) and suicide behavior during treatment, especially at the beginning of a course of treatment or during change of a dose, all patients should be under careful observation.

It is necessary to understand that emergence of some symptoms, such as agitation, the akathisia (which probability of emergence the biggest for the first weeks of treatment) or a mania, can be connected both with the disease course, and with a course of treatment (see the section "Side reactions").

At patients with a clinical aggravation of symptoms (including development of new symptoms) and/or emergence of suicide thoughts / behavior, especially if these symptoms are heavy, arise suddenly or earlier at the patient were not observed, it is necessary to change the mode of administration of drug up to its cancellation.

Serotoninovy syndrome / antipsychotic malignant syndrome.
In isolated cases of treatment paroksetiny can be associated with development of a serotoninovy or antipsychotic malignant syndrome, especially at combined use with other serotonergic and/or antipsychotic drugs. In case of such symptoms as a hyperthermia, rigidity, a myoclonus, vegetative instability with possible bystry fluctuation of the main indicators of a functional condition of an organism, change of the mental status, including confusion of consciousness, irritability, limit agitation with progressing to a delirium and a coma, treatment by Paroksin it is necessary to stop and appoint the supported symptomatic therapy.

Monoamine oxidase inhibitors.
It is necessary to begin treatment by Paroksin with care, not earlier than in 2 weeks after phase-out of MAO inhibitors.

Renal/liver failure.        
It is necessary to appoint drug to patients with expressed renal (the clearance of creatinine - is less than 30 ml/min.) or a liver failure with care as at such patients plasma concentration of a paroksetin increase. In this regard Paroksin's doses should be reduced to minimum effective. Increase in doses and a maintenance dose is adjusted according to clinical effect.

Epilepsy.
Paraxinum, as well as other antidepressants, it is necessary to apply with care at treatment of patients with epilepsy.
In case of emergence at the patient of attacks Paroksin's use needs to be stopped.

Glaucoma.
Paraxinum, as well as other inhibitors of the return serotonin reuptake, can cause a mydriasis therefore it needs to be applied with care to treatment of patients with zakrytouglovy glaucoma.

Hyponatremia.
Cases of development of a hyponatremia, mostly at patients of advanced age were sometimes noted. After phase-out of a paroksetin hyponatremia signs in most cases pass.

Hemorrhages.
Paraxinum needs to be applied with care at treatment of patients which at the same time appointed drugs with the increased risk of emergence of bleeding, and also patients with frequent bleedings in the anamnesis or with tendency to them.

Heart disease.
At treatment of patients with associated diseases of heart it is necessary to adhere to the usual warning measures.

The symptoms observed at cancellation of a paroksetin.
(See the section "Side reactions")

Ability to influence speed of response at control of motor transport or work with other mechanisms.
Paraxinum can cause drowsiness therefore during treatment by Paroksin it is necessary to observe extra care during the driving and work with other mechanisms.

Side effects:

From system of a hemopoiesis: the raised bleeding of skin and mucous membranes (ecchymomas), thrombocytopenia.
From immune system: allergic reactions (including a small tortoiseshell and a Quincke's disease).
From endocrine system: the syndrome caused by insufficient secretion of antidiuretic hormone is possible.
Metabolism and digestive disturbances: increase in level of cholesterol, loss of appetite. Seldom - a hyponatremia. The hyponatremia is observed mainly at patients of advanced age and is sometimes connected with the syndrome caused by insufficient secretion of antidiuretic hormone.
From a digestive tract, a liver: nausea, vomiting, locks, diarrhea, dryness in a mouth. Very seldom - gastrointestinal bleedings. Increase in level of liver enzymes is possible.
Very seldom there are frustration from a liver (such as hepatitises, sometimes with jaundice and/or a liver failure).
From a nervous system and mentality: drowsiness, sleeplessness, agitation, abnormal dreams (including dreadful dreams), confusion of consciousness, a hallucination, maniacal reactions.
Dizziness, tremor, headache, extrapyramidal frustration, epileptic seizures, akathisia, syndrome of uneasy legs. Very seldom - a serotoninovy syndrome (can include agitation, confusion of consciousness, диафорез, hallucinations, a hyperreflexia, a myoclonus, tachycardia and a tremor).
Extrapyramidal frustration, including orofatsialny dystonia, are observed at patients with motive disturbances or at patients who are treated by neuroleptics.
From an organ of sight: decrease in visual acuity, mydriasis, acute glaucoma.
From cardiovascular system: sinus tachycardia, postural hypotension.
From respiratory system: yawning.
From skin and hypodermic fabrics: sweating strengthening, itch, skin rashes, photosensitivity reactions.
From kidneys and urinary tract: urination delay, urine incontience.
Reproductive system: sexual dysfunction, гиперпролактинемия / galactorrhoea.
General frustration: adynamy, increase in body weight, peripheral hypostases.
The symptoms caused by drug withdrawal.

As well as at use of other drugs for treatment of mental disorders, Paroksin's cancellation (especially sudden) can lead to emergence of such symptoms as dizziness, disorder of sensitivity (including paresthesia, a ring in ears), a sleep disorder (including bright dreams), agitation or alarm, nausea, a headache, a tremor, confusion of consciousness, diarrhea and perspiration. At most of patients these symptoms easy or moderate severity also pass without treatment. Symptoms arise usually for the first several days after drug withdrawal, was reported about isolated cases of emergence of such symptoms at patients who inadvertently missed administration of drug. The special risk group of emergence of these symptoms does not exist therefore in case of need Paroksin's cancellations a dose need to be reduced gradually for several weeks or months, depending on specific features of the patient.

Interaction with other medicines:

Serotonergic drugs.
During simultaneous use of Paroksin with lithium, fentanyl, tramadoly or a grass of a St. John's Wort it is necessary to be careful with obligatory careful control of a clinical condition of the patient in order to avoid development of a serotonergic syndrome. For the same reason it is not necessary to appoint Paroksin along with the drugs containing tryptophane and also with other selective serotonin reuptake inhibitors.
Combined use of a paroksetin and MAO inhibitors (including линезолид - an antibiotic which is the MAO return non-selective inhibitor) contraindicated (see the section "Contraindications").

Pimozidum.
Due to the narrow therapeutic index of Pimozidum and its ability to extend QT interval combined use of Pimozidum and paroksetin is contraindicated.

Anticoagulants.
It is necessary to appoint Paraxinum with care along with warfarin and other anticoagulants as their interaction leads to the raised bleeding at not changed prothrombin time.

Drugs with influence on metabolism of enzymes of a liver.
Metabolism and pharmacokinetic parameters of a paroksetin can change at simultaneous use of the drugs inducing or oppressing metabolism of enzymes of a liver.

At simultaneous use of a paroksetin with the drugs inhibiting enzymes it is recommended to appoint the smallest effective doses. At combined use with the drugs inducing enzymes (carbamazepine, rifampicin, phenobarbital, Phenytoinum), there is no need for change of an initial dose of a paroksetin. It is necessary to change a dose throughout further treatment according to clinical effect (portability and efficiency).
As пароксетин actively contacts proteins of plasma, its simultaneous use with other drugs which are actively contacting proteins of plasma can lead to increase in free fraction of one of drugs.

Fosamprenavir/ritonavir.
Combined use of a fosamprenavira/ritonavir with paroksetiny significantly reduces the plasma level of a paroksetin. It is necessary to change a dose throughout further treatment depending on clinical effect (portability and efficiency).

Protsiklidin.
At daily use of a paroksetin the level of a protsiklidin in blood serum considerably increases. In case of anticholinergic effects the dose of a protsiklidin needs to be reduced.

Antikonvulsanta.
Carbamazepine, Phenytoinum, sodium Valproatum. At combined use with these drugs any influence on a drug pharmacokinetics/pharmacodynamics at patients with epilepsy is not observed.

CYP2D6.
Paroksetin slows down activity of P450 CYP2D6 cytochrome. Oppression of CYP2D6 can lead to increase in a blood plasma of concentration of at the same time administered drugs which disintegration catalyzes this enzyme. Some tricyclic antidepressants (for example, amitriptyline, нортриптилин, Imipraminum and desipramine), fenotiazinovy neuroleptics (for example, Perfenazinum and thioridazine), рисперидон, атомоксетин, antiarrhythmic means (for example, пропафенон and флекаинид) and метопролол belong to such drugs.

Paroksetin can reduce efficiency of Tamoxifenum.
Simultaneous use of Paroksin and terfenadin, alprozalam and other drugs which are substrates for CYP3A4 cannot be dangerous.

It is possible to appoint Paraxinum along with a haloperidol, amilobarbitony and oxazepam.
It is established that do not influence absorption or pharmacokinetics of a paroksetin or (that is do not demand dosing change) such factors almost do not influence: food, antacids, digoxin, propranolol, alcohol. However simultaneous use of Paroksin and digoxin has to be carried out with caution in connection with AUC digoxin reduction.

Paroksetin does not strengthen disturbance of the intellectual and motor reactions caused by effect of alcohol however it is not recommended to take alcoholic beverages during treatment by Paroksin. Pharmacological properties.

Contraindications:

Hypersensitivity to a paroksetin or other components of drug.
Paraxinum cannot be accepted along with monoamine oxidase inhibitors (MAO) and earlier than in 2 weeks after the treatment termination by MAO inhibitors.
It is not necessary to apply MAO inhibitors earlier, than in 2 weeks after the termination of treatment by Paroksin.
Paraxinum cannot be accepted along with thioridazine and Pimozidum.
It is contraindicated to children and teenagers up to 18 years.

Overdose:

Therapy paroksetiny is safe with the broad range of doses. Symptoms of overdose arose at a concomitant use of a paroksetin in a dose of 2000 mg or at use of high doses in combination with other drugs or alcohol. Overdose signs - nausea, vomiting, fervescence, change of arterial pressure, involuntary reduction of muscles, uneasiness and tachycardia.

All these effects at patients mostly pass without serious consequences even after reception of a dose of 2000 mg. Sometimes observed a coma or change of the ECG parameters, lethal cases were very seldom noted, but generally in such cases пароксетин it was applied together with other psychotropic drugs or with alcohol.

The specific antidote is unknown.

Treatment. It is necessary to remove drug from a stomach, having caused vomiting or having made a gastric lavage. Carrying out a maintenance therapy at control of the vital indicators and careful observation of a condition of the patient in the conditions of a hospital is shown.

Storage conditions:

To store in the place, unavailable to children, in original packaging at a temperature not over 25 ºС.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister; on 3 or 6 blisters in a cardboard pack.