ВЕЛАКСИН® capsules

General characteristics. Structure:

Active ingredient: each capsule contains 75 mg or 150 mg of a venlafaksin (in the form of a venlafaksin of a hydrochloride).

Excipients: cellulose microcrystallic, sodium chloride, ethyl cellulose, talc, диметикон, potassium chloride, коповидон, silicon dioxide colloid anhydrous, gum xanthane, ferrous oxide yellow. Structure of a gelatin capsule: titanium dioxide, ferrous oxide red, ferrous oxide yellow, gelatin.

Description: Capsules of 75 mg: The solid gelatin self-closed capsules, with the colourless, transparent basis and a cover of orange-brown color, containing mix of pellets of white and yellow color, without or almost inodorous. Capsules of 150 mg: The solid gelatin self-closed capsules, with the colourless, transparent basis and a cover of orange-brown color, containing mix of pellets of white and yellow color, without or almost inodorous.

Pharmacological properties:

Pharmacodynamics. Venlafaksin - antidepressant. On chemical structure it cannot be carried to one known class of antidepressants (tricyclic, tetracyclic or others). It has two active enantiomeric racemic forms. The antidepressive effect of a venlafaksin is connected with strengthening of neyrotransmitterny activity in the central nervous system. Venlafaksin and his main metabolite the O-desmetil Venlafaksin (ODV) are powerful inhibitors of the return serotonin reuptake and noradrenaline and poorly suppress the return capture of dopamine neurons. Venlafaksin and ODV equally effectively influence the return capture of neurotransmitters. Venlafaksin and ODV reduce beta and adrenergic reactions. Venlafaksin has no affinity to muskarinovy, cholinergic, histamine (H1) and α1-адренергическим to brain receptors. Venlafaksin does not suppress activity of monoamine oxidase (MAO). Has no affinity to opiate, benzodiazepine, fentsiklidinovy or N-methyl-d-aspartatnym (NMDA) to receptors.

Pharmacokinetics. After Velaksin's reception, the capsule of the prolonged action, peak concentration of a venlafaksin and O-desmetil a venlafaksin of ODV (the main metabolite) in plasma are reached within 6.0±1.5 and 8.8±2.2 hours, respectively. Speed of absorption of a venlafaksin from capsules of the prolonged action is lower than the speed of its elimination. Therefore, the elimination half-life of a venlafaksin after Velaksin's appointment, the capsule of the prolonged action (15±6 hours) represents, actually, (T1/2) of absorption, than distribution T1/2 (5±2 hours) which is noted after purpose of drug Velaksin tablets. Linkng of a venlafaksin and ODV with proteins of a blood plasma makes respectively 27% and 30%. ODV and other metabolites, and also nemetabolizirovanny венлафаксин, are allocated with kidneys. At repeated introduction equilibrium concentration of a venlafaksin and ODV are reached within 3 days. In the range of daily doses of 75-450 mg, венлафаксин and ODV have linear kinetics. After administration of drug during food time of achievement of the maximum concentration in a blood plasma increases for 20 - 30 minutes, however sizes of the maximum concentration and absorption do not change. Patients with cirrhosis have concentration in a blood plasma of a venlafaksin and ODV are increased, and the speed of their removal is reduced. At a moderate or heavy renal failure the general clearance of a venlafaksin and ODV decreases, and the elimination half-life is extended. Decrease in the general clearance is generally observed at patients with clearance of creatinine lower than 30 ml/min. The age and a sex of the patient do not influence drug pharmacokinetics.

Indications to use:

Depressions (including in the presence of alarm), treatment and prevention of a recurrence.

Route of administration and doses:

Velaksin capsules of the prolonged action should be accepted during food. Each capsule should be swallowed entirely and to wash down with liquid. Capsules cannot be divided, crushed, chewed or placed in water. The daily dose should be accepted at one time (in the morning or in the evening) every time approximately at the same time. Depression:
The recommended initial dose - 75 mg once a day.
If, according to the doctor, higher dose (the heavy depressive frustration or other states demanding hospitalization) is necessary, it is possible to appoint 150 mg at once once a day. Afterwards it is possible to increase a daily dose by 75 mg with an interval two weeks or more (but is not more often than in 4 days), before achievement of desirable therapeutic effect. Maximum daily dose of 350 mg.
After achievement of necessary therapeutic effect the daily dose can be gradually lowered to the minimum effective level.

Maintenance therapy and prevention of a recurrence:
Treatment of a depression has to continue not less than 6 months. At the stabilizing therapy, and also therapy for the purpose of prevention of a recurrence or new episodes of a depression, the doses which showed the efficiency are usually used. The doctor has to regularly (not less once in 3 months) to control efficiency of long therapy by drug Velaksin.

Transfer of patients from tablets Velaksin
The patients accepting drug Velaksin in a dosage form of a tablet can be transferred to administration of drug in a dosage form of the capsule of the prolonged action with purpose of an equivalent dose once a day. However individual correction of a dose can be required.

Renal failure: at a slight renal failure (the glomerular filtration rate (GFR) more than 30 ml/min.) correction of the mode of dosing is not required. At a moderate renal failure (SKF of 10-30 ml/min.) the dose should be lowered by 50%. Due to the lengthening of an elimination half-life of a venlafaksin and its active metabolite (ODV), such patients should accept all dose once a day. It is not recommended to apply венлафаксин at a heavy renal failure (SKF less than 10 ml/min.) as reliable data on such therapy are absent. Patients on a hemodialysis can receive 50% of a usual daily dose of a venlafaksin after end of a hemodialysis.

Liver failure: at a slight liver failure (the prothrombin time (PT) less than 14 sec.) correction of the mode of dosing is not required. At a moderate liver failure (PV from 14 to 18 sec.) should lower a dose by 50%. It is not recommended to apply венлафаксин at a heavy liver failure as reliable data on such therapy are absent.

Elderly patients: advanced age of the patient in itself does not demand change of a dose, however (as well as at purpose of other medicines) at treatment of elderly patients care, for example, in connection with a possibility of a renal failure is required. It is necessary to apply the smallest effective dose. At increase in a dose the patient has to be under careful medical observation.

Children and teenagers (aged up to 18 years):
Safety and efficiency of use of a venlafaksin for children and teenagers are younger than 18 years is not established.

Drug withdrawal Velaksin:
As well as at treatment by other antidepressants, sharp cancellation of reception (especially high doses) of a venlafaksin can cause cancellation symptoms (see the sections "Side Effect" and "Special Instructions"). Therefore before full drug withdrawal the gradual dose decline is recommended. If high doses were applied for more than 6 weeks, it is recommended to reduce doses within not less than 2 weeks. Duration of the period necessary for a dose decline depends on the size of a dose, therapy duration, and also reactions of the patient.

Features of use:

At a depression the risk of suicide thoughts and suicide attempts increases. This risk remains before permanent remission. Therefore patients have to be under constant medical observation and they should give only a small amount of capsules of drug to reduce risk of possible abuse and/or overdose. Velaksin it is not necessary to apply at treatment of children and teenagers 18 years are younger. Increase in probability of suicide behavior (attempt of a suicide and suicide thoughts), and also hostility, in clinical tests is more often observed among the children and teenagers receiving antidepressants in comparison with the groups receiving placebo. It was reported about an agressive behavior during reception of a venlafaksin (especially at the beginning of a course of treatment and after drug withdrawal).

Use of a venlafaksin can cause psychomotor excitement which clinically reminds an akathisia, is characterized by concern with the need to move, is frequent in combination with inability to sit or stand still. It is most often observed for the first several weeks of treatment. At emergence of these symptoms increase in a dose can render an adverse effect and it is necessary to consider a question of expediency of continuation of administration of drug.

As well as all antidepressants, венлафаксин it has to be appointed with care the patient with a mania and/or a hypomania in the anamnesis as drug can cause strengthening of their signs. In these cases medical observation is necessary.

It is necessary to be careful at treatment of patients with convulsive attacks in the anamnesis. During the developing of convulsive attacks or increase in their frequency treatment venlafaksiny should be interrupted.

Like selective inhibitors of the return serotonin reuptake, венлафаксин it is necessary to apply with care at simultaneous use with antipsychotic drugs as the symptoms reminding an antipsychotic malignant syndrome can develop.

Patients should be warned about need to see immediately a doctor when developing rash, small tortoiseshell or other allergic reactions.

At some patients during reception of a venlafaksin dozo-dependent increase in arterial pressure in this connection, regular control of arterial pressure, especially at the beginning of a course of treatment is recommended or at increase in a dose is noted.

During reception of a venlafaksin separate cases of orthostatic hypotension are described. Patients, especially elderly, have to be warned about possibility of dizziness and disturbance of sense of equilibrium.

Venlafaksin can cause increase in frequency of a cordial rhythm, especially during reception of high doses. It is necessary to observe extra care at purpose of drug to patients with states which can amplify at increase in frequency of a cordial rhythm. Sufficient researches of use of a venlafaksin for the patients who recently had a myocardial infarction or having dekompensirovanny heart failure therefore these patients should use this drug with care are not conducted.

As well as other inhibitors of the return serotonin reuptake, венлафаксин the risk of hemorrhages in skin and mucous membranes therefore at treatment of the patients predisposed to bleedings care is necessary can raise.

During reception of a venlafaksin, especially in the conditions of dehydration or decrease in volume of blood (including at the elderly patients and patients accepting diuretics), the hyponatremia and/or a syndrome of insufficient secretion of antidiuretic hormone (SIADH) can be observed. During reception of a venlafaksin mydriasis cases therefore patients with predisposition to increase in intraocular pressure or having risk of closed-angle glaucoma, need careful medical observation are noted. At a renal and liver failure extra care is necessary. In certain cases the dose decline is required (see the section "Route of Administration and Doses"). Safety and efficiency of use of a venlafaksin with the means losing body weight including phentermine, are not established therefore their simultaneous use (as well as use of a venlafaksin as monotherapy for weight reduction of a body) is not recommended. Clinically significant increase in level of cholesterol of blood serum is noted at some patients receiving венлафаксин for not less than 4 months. Therefore at long administration of drug it is reasonable to carry out control of level of cholesterol of blood serum.

After the termination of administration of drug, especially sudden, often there are cancellation symptoms (see the section "Side effect"). The risk of emergence of symptoms of cancellation can depend on several factors, including duration of a course and a dose, and also dose decline speed. Cancellation symptoms such, as: dizziness, touch disturbances (including paresthesias and feelings of passing of electric current), sleep disorders (including sleeplessness and unusual dreams), the excitement or alarm, nausea and/or vomiting, a tremor, perspiration, a headache, diarrhea which is speeded up and the strengthened heartbeat and emotional instability, usually have small or average expressiveness, however some patients can have them heavy. They are usually observed in the first days after drug withdrawal though the patients who accidentally passed one dose had separate messages on emergence of such symptoms. Usually these phenomena pass independently within 2 weeks; however they can be some patients' more long (2-3 months or more). Therefore before cancellation of a venlafaksin it is recommended to lower gradually its dose within several weeks or months depending on a condition of the patient (see the sections "Route of Administration and Doses").

Ability of driving of vehicles

It is necessary to consider that any medicinal therapy by psychoactive drugs can reduce ability of removal of judgments, thinking or performance of motive functions. It is necessary to warn the patient before an initiation of treatment about it. At emergence of such effects degree and duration of restrictions have to be established by the doctor.

Side effects:

The majority of the listed below side effects depend on a dose. At prolonged treatment weight and frequency of the majority of these effects decreases, and there is no need of cancellation of therapy. As decrease in frequency: frequent (<1/10 and> 1/100); infrequent (<1/100 and> 1/1000); rare (<1/1000); very rare (<1/10000)

General symptoms: weakness, fatigue, headache, abdominal pain, fever, fervescence.

From digestive tract: a loss of appetite, a lock, nausea, vomiting, dryness in a mouth; infrequent: bruxism, reversible increase in activity of liver enzymes; rare: gastrointestinal bleeding; very rare: pancreatitis.

From a nervous system: dizziness, sleeplessness, excitement, drowsiness; frequent: unusual dreams, alarm, the confused condition of consciousness, increase in a muscle tone, paresthesia, a tremor; infrequent: apathy, hallucinations, myoclonus; rare: an ataxy, disturbances of the speech, including a dysarthtia, a mania or a hypomania (see the section "Special Instructions"), the manifestations reminding an antipsychotic malignant syndrome, convulsive attacks (see the section "Special Instructions"), a serotonergic syndrome; very rare: nonsense, extrapyramidal frustration, including dyskinesia and dystonia, late dyskinesia, psychomotor excitement / akathisia (see the section "Special Instructions").

From cardiovascular system: arterial hypertension, expansion of blood vessels (rushes of blood), cardiopalmus; infrequent: orthostatic hypotension, faints, tachycardia; very rare: piruetny arrhythmia, lengthening of an interval of QT, ventricular tachycardia, fibrillation of ventricles.

From sense bodys: accommodation disturbances, mydriasis, vision disorder, sonitus; infrequent: disturbance of flavoring feelings.

From system of a hemopoiesis: infrequent: hemorrhages in skin (ecchymomas) and mucous membranes; rare: thrombocytopenia, lengthening of a bleeding time; very rare: agranulocytosis, aplastic anemia, neutropenia, pancytopenia.

From integuments: perspiration, skin itch and rash; infrequent: reactions of a photosensitivity, Quincke's disease, makulo-papular rashes, urticaria; rare: alopecia, mnogoformny erythema, Stephens-Johnson's syndrome.

From urinogenital system: disturbances of an ejaculation, erection, anorgazmiya; infrequent: decrease in a libido, disturbance of a menstrual cycle, menorrhagia, ischuria; rare: galactorrhoea.

From a metabolism: increase in level of cholesterol of blood serum, weight reduction of a body; infrequent: hyponatremia, syndrome of insufficient secretion of antidiuretic hormone, disturbance of laboratory liver function tests; seldom: hepatitis; very rare: increase in level of prolactin.

Musculoskeletal system: arthralgia, mialgiya; infrequent: muscular spasm; very rare: рабдомиолиз.
At children the following side effects were observed: abdominal pain, stethalgia, tachycardia, refusal of food, weight reduction of a body, lock, nausea, ecchymomas, nasal bleeding, mydriasis, mialgiya, dizziness, emotional lability, tremor, hostility and suicide thoughts.
After sharp cancellation of a venlafaksin or decrease in its dose can be observed: fatigue, drowsiness, a headache, nausea, vomiting, anorexia, dryness in a mouth, dizziness, a diarrhea, sleeplessness, concern, alarm, a disorientation, a hypomania, paresthesias, perspiration. These symptoms are usually poorly expressed and pass without treatment. Because of probability of emergence of these symptoms it is very important to reduce gradually a drug dose (as well as any other antidepressant), especially after reception of high doses. Duration of the period necessary for a dose decline depends on the size of a dose, therapy duration, and also individual sensitivity of the patient.

Interaction with other medicines:

Simultaneous use of monoamine oxidase inhibitors (MAO) and venlafaksin contraindicated. Velaksin it is possible to begin administration of drug not less than in 14 days after the end of therapy with MAO inhibitors. If the MAO reversible inhibitor was applied (моклобемид), this interval can be shorter (24 hours). It is possible to begin therapy with MAO inhibitors not less than in 7 days after drug withdrawal Velaksin.

Simultaneous use венлафаксин with lithium can increase the level of the last. At simultaneous use with Imipraminum the pharmacokinetics of a venlafaksin and its metabolite (ODV) will not change. At the same time, their simultaneous use strengthens effects of desipramine - the main metabolite of Imipraminum - and its other metabolite 2-OH Imipraminums though clinical value of this phenomenon is not known.

Haloperidol: Combined use increases haloperidol level in blood and strengthens its effects.

At simultaneous use with diazepam the pharmacokinetics of drugs and their main metabolites, significantly do not change. Also influence on psychomotor and psychometric effects of diazepam is not revealed.

At simultaneous use with clozapine increase in its level in a blood plasma and development of side effects can be observed (for example, convulsive attacks). At simultaneous use with risperidony (despite increase in AUC of a risperidon) the pharmacokinetics of the sum of active components (a risperidon and its active metabolite) significantly does not change.

Decrease in an intellectual and physical activity under the influence of alcohol amplified after the prima of a venlafaksin. Despite it - as well as in case of reception of other drugs influencing the central nervous system - during therapy venlafaksiny the use of alcoholic beverages is not recommended.

Against the background of reception of a venlafaksin it is necessary to observe extra care at electroconvulsive therapy as experience of use of a venlafaksin in these conditions is absent. Medicines, metaboliziruyemy isoenzymes of P 450 cytochrome: CYP2D6 enzyme of system of P 450 cytochrome will transform венлафаксин to an active metabolite of ODV. Unlike many other antidepressants, the dose of a venlafaksin can be not reduced at simultaneous introduction with the drugs suppressing activity of CYP2D6 or patients with genetically caused decrease of the activity have CYP2D6 as total concentration of a venlafaksin and ODV at the same time will not change.
The main way of removal of a venlafaksin includes metabolism with participation of CYP2D6 and CYP3A4; therefore it is necessary to observe extra care at purpose of a venlafaksin in combination with the medicines oppressing both of these enzymes. Such medicinal interactions are not investigated yet.

Venlafaksin - rather weak CYP2D6 inhibitor also does not suppress activity of isoenzymes of CYP1A2, CYP2C9 and CYP3A4; therefore it is not necessary to expect it interaction with other drugs in which metabolism these liver enzymes participate. Cimetidinum suppresses metabolism of "the first passing" of a venlafaksin and does not exert impact on ODV pharmacokinetics. At most of patients only slight increase of the general pharmacological activity of a venlafaksin and ODV is expected (it is more expressed at elderly patients and at an abnormal liver function).

Clinical trials did not find clinically significant interactions of a venlafaksin with anti-hypertensive (including beta-blockers, APF inhibitors and diuretics) and antidiabetic drugs.

The medicines connected with proteins of a blood plasma: linkng with proteins of plasma makes 27% for a venlafaksin and 30% for ODV therefore it is not necessary to expect the medicinal interactions caused by linkng with proteins.

At a concomitant use with warfarin, the anticoagulating effect of the last can amplify, at the same time the prothrombin time is extended and MHO raises. At a concomitant use with indinaviry the pharmacokinetics of an indinavir changes (with 28% reduction of AUC and 36% decrease in Cmax), and the pharmacokinetics of a venlafaksin and ODV does not change. However clinical value of this effect is unknown.

Contraindications:

Hypersensitivity to any component of drug. A concomitant use of MAO inhibitors (see also section "Interaction"). Heavy renal failures and/or liver (SKF less than 10 ml/min., PV more than 18 sec.). Age up to 18 years (safety and efficiency for this age group are not proved). Pregnancy or alleged pregnancy. The lactation period (there are no sufficient data of controlled researches).

Overdose:

Symptoms: changes of an ECG (lengthening of an interval of QT, blockade of a leg of a ventriculonector, expansion of the QRS complex), sinus or ventricular tachycardia, bradycardia, arterial hypotension, convulsive states, consciousness oppression (decrease in level of wakefulness). At overdose of a venlafaksin at a concomitant use with alcohol and/or other psychotropic drugs, it was reported about a lethal outcome.

Treatment: symptomatic. Specific antidotes are unknown. Continuous control of the vital functions (breath and blood circulation) is recommended. Purpose of absorbent carbon for decrease in absorption of drug. It is not recommended to cause vomiting in connection with danger of aspiration. Venlafaksin and ODV are not removed at dialysis.

Storage conditions:

Period of storage 2 years. Not to use after the expiration date of a period of storage specified on a box. To store at a temperature below 30 °C in the dry place. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 or 14 capsules in the blister from PVH/PVDH/al.folga. 2 blisters on 14 capsules or 3 blisters on 10 capsules together with the instruction on a medical use in a cardboard pack.