Active matter: Paroxetine (hydrochloride hemihydrate) 20 mg

Auxiliary matters: calcium phosphate diatomic (dihydrate), sodium starch (type A), magnesium stearate, magnesium stearate, Opadry White YS-1R-7003 (hypromellose, titanium dioxide (E 171), polyethylene glycol 400, polysorbate 80).

Tablets are covered by the tunic.

The main physical-chemical properties are white color, covered by the tunic, oval convexo-convex pills with marking «20» from one side and line of distribution from other side.

Psychoactivators (or psychoactive substances). Antidepressants. Selective inhibitors of the reversible neuronal capture of serotonin. Code АТХ N06A B05.

Pharmacological:

Paxil is a powerful selective serotonin reuptake inhibitors (5-HT). Its anti-depressed action and effectiveness under the medical cure of obsessive-compulsive and panic disorders is conditioned by the specific braking of 5-hydroxytryptamine reuptake by the brains neurons. By its chemical structure Paxil is differed from the tricyclic, tetracyclic and other well-known antidepressants. Medication has lower affinity with muscarinic cholinoreceptors. As opposed to tricyclic antidepressants this medication has insignificant affinity with alpha 1-, alpha 2-  and beta-adrenoreceptors, dopamine (D2), 5-НТ 1 figurative, 5-НТ 2- and histaminic (H 1-) receptors. The preparation doesn’t influence on the psychomotor function and it doesn’t strengthen the depressing action of ethanol.

Paxil doesn’t influence on the activity of cardiovascular system. It doesn’t call ant clinically meaningful exchanges of arterial pressure, frequency of cardiac shortenings and ECG parameters.

Pharmacokinetics:

This drug is absorbed quickly after its applying and it is subjected for the transformation in liver.

The main metabolites of Paroxetine (main active matter) are polar and conjugate products of oxidation which are quickly taken away from organism.

About 64% of Paroxetine dose is taken away with urine and about 36% of Paroxetine applied dosage is taken away with feces in view of metabolites.

The period of semi ejection is about one day.

The constant concentration in blood is reached over 7-14 days after the treatment beginning and in following prolonged medical cure the pharmacokinetics of the drug isn’t practically changed. It wasn’t exposed any correlation between Paroxetine concentration in blood plasma and clinical effect. Under the increasing of single dosage or under the repeated dosing it can be appeared some effects of metabolic way’s partial satiation of the first passing through liver and it is observed the clearance lowering. That brings to the disproportionate elimination of Paroxetine concentration in blood plasma and some exchanges of pharmacokinetic parameters with appearance of non-linear dependence.

Paroxetine is widely distributed in the tissues of organism. Under the applying in therapeutical dosages approximately95% of Paroxetine is tied together with proteins of blood plasma.

It is observed the increasing of Paroxetine concentration in blood plasma by aged patients and sick individuals with renal and hepatic insufficiency.

Treatment of the large depressed disorder, obsessive-compulsive disorder (treatment of symptoms and prevention of relapses), panic disorders (with or without agoraphobia), social phobia, social-anxious disorders, generalized anxious disorder, posttraumatic stressed disorder.

Paxil is contra-indicated by the patients with hypersensitivity to Paroxetine or to each other components entered into the structure of this medical preparation.

The drug is also contraindicated for patients with convulsions or for sick persons who have suddenly stopped the applying of alcohol or some sedative medications in presence time.

It isn’t followed to prescribe Paxil together with MAO inhibitors including Linezolid – antibiotic which is reversible nonselective inhibitor of MAO and Metiltionin hydrochloride and not earlier than over 2 weeks after the treatment stopping by MAO inhibitors. Paxil isn’t taken together with Thioridazine (antipsychotic drug).

Synchronous applying of Paxil with other serotonin-containing medications (serotonin-ergic drugs) can bring to 5-НТ-associated effect (serotonin syndrome). Paxil isn’t applied together with MAO inhibitors and some medications from this medical class.

Metabolism and pharmacokinetics of Paroxetine can be changed under the influencing of induction or inhibition of some ferments taken part into metabolism of officinal agents. It is recommended to prescribe the minimal effective dosages under the synchronous application of Paroxetine together with preparations which inhibit the ferments.

The synchronous applying of this substance together with medications which are metabolized mostly by this ferment (such as separate b-blockers, antiarrhythmic drugs, selective inhibitors of serotonin’s reversible capture, tricyclic antidepressants, antipsychotic remedies) is followed to begin from minimal dosages of accompanied preparation. If Paxil is included into the treating scheme of sick individual which have already given this medical agent metabolized by CYP2D6 it is followed to estimate the necessity of dose diminishing of this medication especially for the medical remedies with wide therapeutical index.

As far as Paroxetine is intensively metabolized the synchronous prescribing of medical preparations strengthened the metabolism (for example, Carbamazepine, Phenobarbital, Phenitoin, Ritonavir, Ephavirense) or suppressed metabolism can change its clinical activity.

By the data of clinical researches the medications as Ritonavir (100 mg twice per day or 600 mg 2 twice per day) or Ritonavir 100 mg and Lopinavir 400 mg twice a day had dose-dependently diminished the concentration of Paroxetine and its main metabolites approximately on 20-80%. In such case the medication as Ephavirense 600 mg once a day during two weeks diminishes the concentration of Paroxetine approximately on 65%. This effect of Ritonavir / Lopinavir and Ephavirense is tied together with induction of Paroxetine metabolism. The patients who are treated by each of these medical preparations together with medicaments contained the matter as Paroxetine in their structure can be needed the dosage increasing but it is impossibly to heightened the maximal recommended doses.

SSRIs can lower the activity of blood plasma choline esterase that brings to the increasing of neuromuscular blocking action of mivakurium and suxametonium.

Children and teenagers

The treatment by antidepressants is usually associated with heightened risk of suicidal ideas and behavior by children and teenager with heavy depressed and other psychical disorders.

Worsening of clinical condition and risk of suicide by adults

Adults with heavy depressed and other psychical disorders can have heightened risk of suicidal behavior appearance during the treatment by Paxil. It can be sharpened the symptoms of depression and / or formed the suicidal ideas and behavior by patients with depressed disorders independently of applying or not applying of antidepressants. This risk is kept till full remission. The general clinical experiment of treatment by all courses of antidepressants is growing of suicides risk in the earliest stages of remission.

Hepatic / renal insufficiency

It is recommended the applying of Paxil with prudence by the patients with heavy hepatic or renal insufficiency

Diabetes mellitus

It is necessary to correct the dosage of insulin and / or per oral anti-diabetic preparation under the synchronous application of these drugs together with SSRIs. The clinical researches show that glucose level in blood can be observed under the synchronous treatment by Paroxetine and Pravastatine.

Epilepsy

Paxil as other antidepressants is followed to apply with prudence under the treatment of sick persons with epilepsy.

Glaucoma

The mydriatic pupils that is usually happened after some using of different antidepressants including Paxil can bring the crisis of narrow-angle glaucoma by sick individuals with anatomically narrow angle.

Reactions of hypersensibility

It is followed to stop the application of Paxil if it was appeared some symptoms of hypersensibility by the patient during the medical cure by this drug.

Hyponatremia

Sometimes it is registered the cases of hyponatremia development mainly by aged ill persons/ After the medication withdrawal the reasons of hyponatremia are mostly stopped.

Cardiac sicknesses

It is followed to observe the usual measures of precaution under the treatment with Paxil by patients with different diseases of heart.

Convulsions

The recommended dosage of Paxil isn’t followed to increase because the dose-depended development of convulsions is typical for Paroxetine. In doses which aren’t heightened maximally recommended daily norm (till 60 mg of Paxil per day) the frequency of the convulsion development is about 0,1% (1/1000).

The risk of convulsions development tied together with Paxil applying intimately correlates with presence of the risk’s factors. So this medical preparation is prescribed with some prudence for patients who have one or several such factors promoted to some lowering of the convulsive readiness’s threshold.

Besides it is followed to be careful in some clinical cases tied together with vessels’ heightening risk. They include the alcohol abuse, some stimulators of the central nervous system or different sedative medications, diabetes mellitus, for curing of which it is applied the sugar-lowering preparations and insulin, arterial-venous malformations, infections of the central nervous system, metabolic discomposing (hypoxemia), heavy stroke, applying of opiates, stimulators or anorexants. It is followed to abolish the drug of Paxil and it isn’t followed to applying this medication secondary for the patients who is observed the convulsive attacks during the treatment.

Social phobia and panic disorders

There is some information about symptoms development of social phobia and panic disorders Particularly by the patients with some psychical sicknesses it is observed the psychotic and maniacal symptomatology. Additionally the heavy depressed episode can be the beginning manifestation of the bipolar disorder. There is a generally accepted opinion (it isn’t corroborated by any clinical researches) that the treatment of such episodes by different antidepressants independently can increase the possibility of mixed / maniacal episodes strengthening by sick people with some risks of the bipolar disorders’ development. The limited clinical data about Bupropion using in combination with mood stabilizers by patients with bipolar upset in anamnesis allow supposing the lowest degree of mania appearance. The sick persons must take an adequate inspection with a goal of risk identification of bipolar disorders appearance till the beginning of the medical cure by antidepressants. Such inspection includes the collection of detailed psychiatric anamnesis including anamnesis by the members of a family about the presence of suicides, bipolar disorders and depressions.

The treatment by antidepressants is tied together with heightened risk of suicidal ideas manifestations and appearance of the inadequate behavior by the children and teenagers which are sick in depressing and other psychical disorders.

Symptomatology worsening

It can be worsened the symptomatology of depressed condition and / or capability to some perception and formation of suicidal ideas and behavior independently from applying of different antidepressants by sick persons with depression. The risk of this fact stays during all time till remission beginning. As far as some improvement of condition cannot begin during the first weeks (or more) of the medical cure the patient must by under the observation with a goal of the reasons exposure of condition’s clinical worsening (including the appearance of the new symptoms) or suicidal ideas and behavior especially in the beginning if the treating course or under the dosages exchanging as increasing as diminishing ones. Taking into account the general clinical test it is considered that under all antidepressants using there is some risk of suicides increasing on the early stages of recovery.

The patients with suicidal behavior or expectancies in anamnesis and the young patients manifest in larger degree the capability to the formation and perception of suicidal ideas till the medical cure beginning. They are the group of big risk for suicidal ideas and suicidal attempts that’s why they must be under the careful controlling during the treatment.

The patients must be anticipated about the necessity of the careful control for every worsening of their condition (including the new symptoms appearance) and / or appearance of suicidal ideas / behavior or intentions to harm theirselves. In cases of such symptoms appearance it is followed to appeal for the medical helping immediately. It is followed to take into account that appearance of neuropsychic symptoms can be tied together such with main sickness as with preparation applying.

The sick persons with worsening of condition (including the development of new symptoms) and / or appearance of suicidal ideas / behavior (especially if these symptoms have the heavy form) arise suddenly or not the part of the present symptoms needed in the substitute pf treatment’s therapeutic regime taken into account the medical cure stopping.

Arterial pressure

In clinical research with taking part of some sick persons which aren’t ill on depression (including such patients who smoke as people who don’t smoke) and have not treated stage of arterial hypertension the applying of Paroxetine didn’t bring to statically meaningful influence on the arterial pressure. But it is also observed the spontaneous reports about heightening of arterial pressure sometimes in view of side effects or overdosing. The synchronous usage of Paroxetine and nicotinic transdermal system can bring to the arterial pressure heightening.

Insufficient ways of introduction

Paroxetine is prescribed for using per orally only. There are some reports about inhalation of crushed pills or injection of Paroxetine dissolution which can bring to the quickest deblocking, accelerated absorption and potential overdosing. There are also some information about epileptic attacks and / or lethal cases (patients’ death) when Paroxetine was brought intranasal pr by the way of parenteral injection.

Fertility:

By the data of some clinical researches it was showed that selective inhibitors of serotonin reversible capture including Paxil can influence on the sperm quantity. It is considered that all these phenomena pass after the treatment stopping. Some exchanges of sperm qualitative characteristics can influence on the some male persons’ fertility.

Pregnancy:

After some epidemiological researches of influencing on the gestation it was reported about associated risk of the development of cardio-vascular system’s intrauterine pathology by fetus under Bupropion application of pregnant woman in the first term. These data were identical ones in different researches.

Physician must consider the possibility of the alternative treatment of the pregnant person or woman planned the gestation and he has to prescribe Wellbutrin SR only in cases when the waited benefit from the medical cure heightened the potential risk.

According to the data of pregnancy international register the indicators of the inherent cardiac defects under Bupropion application in the first term are 9/675 (1,3%).

Breast-feeding:

Some quantity of Paxil is taken away into the breast milk. It wasn’t revealed any reasons of this preparation influencing on the newborns but it isn’t followed to apply the medication as Paxil in period of breast-feeding besides the cases when the waited benefit for mother is heightened the possible risk for baby.

As other medicaments with anti-depressed effect mainly influenced on the person’s central nervous system the substance as Paroxetine can influence on the capability to implement some tasks needed the heightened attention and movement coordination. That’s why the patients must observe some care under car driving and some other mechanisms controlling to make sure that Paxil doesn’t disturb their functions.

Medication doesn’t strengthen any damages of mental and motor reactions called by the alcohol applying but it isn’t recommended the synchronous application of Paxil and alcohol in any dosages.

general recommendations

Medication is indicated for per oral applying. It is recommended using of this drug once per day – during the eating in the morning. It is followed to swallow up the tablet not masticated. The pill has a line of breaking that allows to get the dosage of 10 mg under the necessity.

Such by other anti-depressed agents the dosing of this medication is followed to pick up individually only by the medical specialist during the first 2-3 weeks and then the dosage can be corrected in dependence of clinical manifestations.

The course of treatment must be enough prolonged and enough for supplying of symptoms elimination. This period can be prolonged during several months under the medical cure of large depressed disorder and under the obsessive-compulsive or panic disorder the period of treatment can be lasted more. It is followed to avoid the sudden withdrawal of this medical preparation as under the applying of other drugs used for psychical disorders treating.

large depressed disorder

The recommended dosage is 20 mg per day. For treatment of some sick individuals it can be needed the dosage increasing. The dosage is usually increased step by step enlarged on 10 mg (maximally till 50 mg a day) in dependence of treatment’s clinical effectiveness.

obsessive-compulsive disorder

The recommended dosage is 40 mg per day. It is followed to begin the medical cure from dosage as 20 mg per day and then the daily norm is increased on 10 mg per day step by step. It is usually observed the condition improvement by some patients only under the applying of Paxil maximal dosing as 60 mg per day.

panic disorder

The recommended dosage is 40 mg per day. It is followed to begin the medical cure from dosage as 10 mg per day and then the daily norm is increased on 10 mg per day step by step in dependence of clinical effect. It is usually observed the condition improvement by some patients only under the applying of Paxil maximal dosing as 60 mg per day.

It is recommended to start the medical cure from small dose of this medication for diminishing of the risk of panic disorder’s symptomatology possible strengthening.

social-anxious disorders / social phobia

The recommended dosage is 20 mg per day. For treatment of some sick individuals it can be needed the dosage increasing. The dosage is usually increased step by step enlarged on 10 mg (maximally till 50 mg a day) in dependence of treatment’s clinical effectiveness. The interval between the dosages increasing must be not less than a week.

generalized anxious disorder

The recommended dosage is 20 mg per day. For treatment of some sick individuals it can be needed the dosage increasing. The dosage is usually increased step by step enlarged on 10 mg (maximally till 50 mg a day) in dependence of treatment’s clinical effectiveness.

posttraumatic stressed disorder

The recommended dosage is 20 mg per day. For treatment of some sick individuals it can be needed the dosage increasing. The dosage is usually increased step by step enlarged on 10 mg (maximally till 50 mg a day) in dependence of treatment’s clinical effectiveness.

preparation withdrawal

As under the application of other medication for medical cure of different psychical sicknesses it is followed to avoid the sudden withdrawal of this medicament. During the clinical researches it is used the regime of gradual lowering of the preparation dose which includes the decreasing of daily norm on 10 mg per day with interval of a month. After the achievement of dosing regime as 20 mg the sick persons took this medication in such dosage during a week before its full withdrawal. In case of powerfully expressed symptoms appearance during the dosage lowering or after treatment withdrawal it is followed to settle the issue about treatment recovery in previous dose. Later the patient can continue the dosing decreasing but less slowly.

aged patients

The treatment by this medication must be started from usual beginning dosage for adults which can be gradually increased till 40 mg per day. It is fixed some cases of heightened concentrations of Paroxetine in blood plasma by patients of elderly age but the diapason of these concentrations by this group of patients coincides with following diapason by the patients of elder age.

patients with damages of liver and kidneys’  function

It is observed some heightening of Paroxetine concentration in blood plasma by the patients with expressed renal insufficiency (the clearance of Creatinine is less than 30 ml / min) or hepatic insufficiency. That’s why for such patients it is followed to diminish the dosage till lower border of dosing diapason.

children

Paxil isn’t indicated for the medical cure of children.

By the results of controlling clinical researches it wasn’t registered any effectiveness and it also wasn’t gotten any confirmed data about Paxil applying by the children who were sick on depression. Safety and effectiveness of this medical preparation for children till seven years isn’t researched.

In case of Paxil overdosing (besides the symptoms described in the category «Side effects») it is observed the body temperature heightening, some exchanges of arterial pressure, involuntary shortening of muscles, anxiety and tachycardia.

All these effects by patient are mainly conducted without any heavy consequences even after the application of dosage as 2000 mg. Sometimes it is observed the coma or some exchanges of the ECG parameters; it is rarely observed the lethal cases but mainly in such cases the medication as Paxil was applied with other psychotropic preparation and sometimes with alcohol.

The specific antidote is unknown.

The overdose treatment must include the general therapeutical measures such as under the overdosing by other antidepressants. It is also showed the conduction of supporting treatment with controlling of vital important indicators and careful observation for the sick person condition.

By the results of clinical applying the side effects are systematized by the organs and systems and frequency of appearance. By the frequency of appearance all collateral results are divided into very often (≥ 1 on 10), often (≥ 1 on 100 and <1 on 10), not often (≥ 1 on 1000 and <1 on 100), seldom (≥ 1 on 10000 and <1 on 1000), very seldom <(1 on 10000), unknown (by having data the frequency is impossible to define).

The patients applied Paxil can have some exchanges of psychical conditions, mania or hypomania.

From the side of blood and lymphatic system*

Seldom: heightened hemorrhagic diathesis mainly by skin and mucous covers (including ecchymosis and gynecological hemorrhages).

Very seldom: thrombocytopenia.

From the side of immune system*

Very seldom: heavy and potentially lethal allergic reactions (including anaphylactoid reactions and angioneurotic edema).

From the side of endocrinic system*

Very seldom: syndrome conditioned by the insufficient secretion of ADH.

From the side of metabolism and disorders of digestion*

Often: anorexia.

Not often: body weight decreasing. If the body weight decreasing is the largest symptom of patient’s depression it is followed to take into account such potentials of Wellbutrin SR as anorexia and / or body weight decreasing.

Very seldom: discomposing of the glucose level on blood.

From the side of psychics*

Very often: insomnia, sleepiness, agitation, anomalous dreams (including night fears).

Unknown: sleeping damages, euphoria, mania, hypomania, some exchanges of the psychical condition.

Often: excitation, mental confusion, stimulation, anxiety, hallucinations.

Not often: depression, dysphoria, random orientation.

Very seldom: aggression, hostility, irritability, uneasiness, unusual dreams, depersonalization, delirium, paranoid thoughts.

Frequency is unknown: suicidal ideas and suicidal behavior, psychosis.

From the side of the central nervous system*

Very often: headaches.

Often: tremor, dizziness, taste discomposing, memory damages, nervousness, agitation, anxiety, myoclonus, dystonia, migraine.

Not often: disorders of the attention concentration, vertigo, acathisia, dysarthria.

Seldom: convulsions, damages of ECG.

Very seldom: dystonia, ataxia, parkinsonism, disorders of the movements’ coordination, memory discomposing, paresthesia, fainting fit.

Unknown: coma, delirium, damages of the apprehensibility, dyskinesia.

From the side of visual organs*

Often: visual disorders.

Seldom: diplopia.

Not often: mydriasis.

Unknown: heightening of eyes pressure.

From the side of hearing organs*

Often: ringing in the ears.

From the side of cardiovascular system*

Not often: sinus tachycardia, orthostatic hypotension, damages of the cardiac rhythm, some changes of ECG, transistor heightening or lowering of the arterial pressure

Seldom: myocardial infarction.

Unknown: edemas.

Very seldom: the strongest palpitation, bradycardia.

From the side of respiratory system*

Seldom: pulmonary embolism.

Unknown: bronchitis.

From the side of vessels*

Often: heightening of the arterial pressure (in some case it can be considerable one), reddening.

Very seldom: vasodilation, orthostatic hypotension.

From the side of gastrointestinal tract*

Very often: dryness in mouth, gastrointestinal disorders including nausea and vomiting.

Often: some pains in stomach, constipation, dyspepsia.

Not often: toothaches, gums irritation.

Unknown: perforation of the bowels.

Very seldom: heightening of the hepatic ferments’ level, jaundice, hepatitis.

From the side of skin and hypodermic tissue*

Often: precipitation, itching, hyperhidrosis.

Very often: polymorphous erythema, Stevens-Johnson syndrome, psoriasis sharpening.

Unknown: alopecia.

From the side of hepatobiliary system*

Seldom: heightening of the hepatic ferments’ level.

Very seldom: discomposing from the side of liver (such as hepatitis, sometimes with jaundice and / or hepatic insufficiency).

There is some information about the hepatic ferment’s level heightening. It is also rarely reported about side effects from the side of liver (such as hepatitis sometimes tied together with jaundice and / or hepatic insufficiency). It is necessary to be considered the possibility of the Paroxetine applying stopping if the heightening of the hepatic tests would be kept.

From the side of kidneys and urogenital system*

Often: infections of the urogenital system.

Not often: libido lowering.

Very seldom: increasing of the urination frequency and / or its delay.

Unknown: erectile dysfunction, damages of the menstrual cycle, gynecomastia, testicles edema, glycosuria, nocturia.

From the side of locomotive apparatus and connecting tissues*

Very seldom: vellication or muscle convulsions.

Unknown: arthritis, arthrosis.

Some epidemiological researches passed mostly among the patients in age of 50 years old are testified about the heightened risk of bones breaking by sick persons applied the medications as SSRIs and tricyclic antidepressants. The mechanism brought to this risk is unknown.

General disorders*

Often: asthenia, body weight increasing.

Very seldom: peripheral edemas.

Symptoms conditioned by the medication withdrawal*

Often: dizziness, disorders of the apprehensibility, sleeping discomposing, uneasiness, headaches.

Seldom: agitation, nausea, tremor, mental confusion, hyperhidrosis, diarrhea, emotional instability, visual disorders, strengthening heartbeat (tachycardia), irritability.

As under the application of other medical preparations for treatment of psychical disorders Paxil withdrawal (especially unusual one) can bring to the appearance of such symptoms as dizziness, disorders of the apprehensibility (including paresthesia, sensation of electric shock  and noising in ears), sleeping discomposing (including intensive night dreams), agitation or uneasiness, headaches, nausea, tremor, mental confusion, hyperhidrosis, diarrhea, visual disorders, strengthening heartbeat (tachycardia), irritability, emotional instability. The biggest number of patient has these sicknesses and disorders in light or medium forms and they aren’t needed any treatment. In any case the dosing of Paxil must be lowered step by step and only after the consultation with a medical specialist.

Side effects given under the conduction of clinical researches by the applying of these medicines by children*

Under the conducting of clinical researches by this preparation applying by some children is was gotten the following side effects as emotional lability (including harming to theirselves, suicidal ideas, crying with some threat of self-murder and mood exchanges), hostility, appetite lowering, tremor, heightened perspiration, hyperkinesia and agitation. The suicidal ideas and some attempts of self-murder are observed mainly during the clinical researches under the treatment of teenagers with different depressing disorders. The hostility is observed mostly by the children with obsessive-compulsive disorder especially by children in age till twelve years old.

Under the conducting of clinical researches with applying of gradual dosing lowering regime (diminishing of the daily norm on 10 mg / day with interval of one week in dosing 10 mg / day during a week) or after the medication withdrawal it is observed such symptoms as emotional lability, nervousness, dizziness, nausea and some pains in abdomen.

Three years

It is followed to keep these medicines under the temperature not higher than 30 °С in original package. Keep this drug in place too difficult for children.

By 14 pills in blister, by 2 blisters in the box.

Paroxetine