Venzuert - instructions for use, dose, side effects, contraindications

auxiliary ingredients: cellulose microcrystalline 62.45 mg, hypromellose 0.37 mg, water purified qs, ethyl cellulose 16.26 mg, povidone 4.07 mg, triacetin 0.2 mg, isopropanol * qs, methylene chloride * qs, talc purified 0.97 mg ;

capsule shell: body: iron dye oxide red 0.030%, titanium dioxide 1.300%, water 14.500%, sodium lauryl sulfate 0.080%, gelatin 84.09%; lid: dye, brilliant blue 0.0190%, dye quinoline yellow 0.0166%, dye red charming 0.036%, titanium dioxide 1.9500%, gelatin 83.39%, water 14.50%, sodium lauryl sulfate 0.080%.

Dosage of 75 mg:

active ingredient: venlafaxine hydrochloride 84.855 mg, equivalent to venlafaxine 75 mg;

auxiliary ingredients: cellulose microcrystalline 124.895 mg, hypromellose 0.75 mg, purified water q.s., ethyl cellulose 32.515 mg, povidone 8.13 mg, triacetin 0.405 mg, isopropanol * q.s., methylene chloride * q.s., talc purified 1.95 mg;

shell capsules: body: iron dye oxide red 0.015%, titanium dioxide 1.1373%, water 14.500%, sodium lauryl sulfate 0.080%, gelatin 84.26%; cap: iron dye oxide red 0.015%, titanium dioxide 1.1373%, water 14.50%, sodium lauryl sulfate 0.080%, gelatin 84.26%.

Dosage of 150 mg:

active ingredient: venlafaxine hydrochloride 169.71 mg equivalent to venlafaxine 150 mg;

auxiliary ingredients: cellulose, microcrystalline 249.79 mg, hypromellose 1.5 mg, purified water qs, ethylcellulose 65.03 mg, povidone 16.26 mg, triacetine 0.81 mg, isopropanol * qs, methylene chloride * qs, talc purified 3.9 mg ;

shell capsules: lid: dye iron oxide red 1.333%, iron dye oxide yellow 0.1333%; titanium dioxide 0.2167%, water 14.500%, sodium lauryl sulfate 0.0800%, gelatin 83.73%; body: dye iron oxide red 1.333%, iron oxide dye yellow 0.1332%, titanium dioxide 0.2167%, water 14.500%, sodium lauryl sulfate 0.0800%, gelatin 83.73%.

Ink for inscription (TEK 9008 black) is used for all dosages: Shellac 24-27%, dehydrated, alcohol 23-26%, isopropanol 1-3%, butanol 1-3%, propylene glycol 3-7%, ammonia solution concentrated 1-2%, iron dye oxide black 24-28%, potassium hydroxide 0.05-0.1%, purified water 15-18%.

* - evaporates in the production process.

Description:

Capsules 37.5 mg

Hard gelatinous opaque capsules No. 2, capsule body of light pink color with the inscription "37.5"; a gray lid with the inscription "RVn". Contents of capsules: from white to almost white color spherical granules.

Capsules 75 mg

Hard gelatinous opaque capsules No. 1, capsule body of light pink color with the inscription "75"; The lid is a light pink color with the inscription "RVn".Contents of capsules: from white to almost white color spherical granules.

Capsules 150 mg

Hard gelatinous opaque capsules No. 0, body of a capsule of dark orange color with the inscription "150"; lid of dark orange color, with the inscription "RVn". Contents of capsules: from white to almost white color spherical granules.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Venlafaxine is an antidepressant, which is a racemate with two active enantiomers. The mechanism of antidepressant action of venlafaxine is associated with its potentiating effect on neurotransmitter activity in the central nervous system. Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA), are potent inhibitors of serotonin and norepinephrine reuptake and weak inhibitors, re-uptake of dopamine. On the inhibition of serotonin reuptake venlafaxine is inferior to selective serotonin reuptake inhibitors.

Pharmacokinetics:

Absorption - at least 92% of the once-ingested dose of venlafaxine. The absolute bioavailability of venlafaxine is about 45%.After a single administration of capsules of venlafaxine, the maximum concentration (C_m_Oh) of venlafaxine and EFA in plasma is achieved within 6.0 ± 1.5 and 8.8 ± 2.2 hours, respectively. The half-life of venlafaxine in the dosage form of the "prolonged-action capsule" is 15 ± 6 hours and is limited by the rate of absorption.

Distribution. Venlafaxine and EFA are 27% and 30% respectively associated with plasma proteins.

Metabolism. Venlafaxine undergoes a marked metabolism of the "first passage" in the liver with the participation of cytochrome P450 (isoenzyme CYP2D6) to form an active metabolite of EFA. Venlafaxine It is also metabolized by CYP3A3 / 4 isoenzymes to N-desmethylvenlafaxine and other metabolites. In patients with a decreased activity of the isoenzyme CYP2D6, there is a 2-3-fold greater exposure of venlafaxine and a 2-3-fold lower exposure of the active metabolite of EFA.

Excretion. The venlafaxine clearance in blood plasma is 1.3 l / h / kg, and for the active metabolite of EFA it is 0.4 l / h / kg. The half-life of venlafaxine is 15 hours and EFA is 11 hours.

Venlafaxine is excreted mainly by the kidneys, about 87% within 48 hours, unchanged - 5%, in the form of unconjugated EFA - 29%, conjugated EFA - 26% and other inactive metabolites - 27%.There is no accumulation of venlafaxine or EFA during long-term use.

Special patient groups

Sex and age do not significantly affect the pharmacokinetics of venlafaxine.

With hepatic and renal insufficiency from medium to severe degree, as well as in individuals with low activity decreased venlafaxine metabolism and elimination of EFA, which resulted in an increase in C_m_Oh, reduced clearance and an elongated half-life. The decrease in the total clearance of venlafaxine is most pronounced in patients with creatinine clearance (CC) below 30 ml / min. Taking venlafaxine with food does not affect the absorption of venlafaxine, nor the subsequent formation of EFA.

In patients with a low activity of the isoenzyme CYP2D6 the concentration of venlafaxine in the blood plasma is higher than that of the main metabolites. Due to the fact that the area of the pharmacokinetic curve (AUC) of venlafaxine and EFA in patients with low and high metabolic rate is almost the same, there is no need to select individual dose groups for these groups of patients.

In patients on renal dialysis, the half-life of venlafaxine is increased by 180%, and venlafaxine clearance is reduced by approximately 57%, while the half-life of EFA is increased by 142%, and the clearance is reduced by 56%.The selection of individual doses of venlafaxine is necessary for patients with severe renal failure and for patients on hemodialysis.

In patients with mild to moderate hepatic impairment On the Child-Pugh scale, the half-life of venlafaxine and EFA is higher. The clearance of venlafaxine and EFA when taking the drug inside is reduced, and the decrease is possible in a very wide range and is of an individual character. Data on pharmacokinetics in patients with severe hepatic insufficiency on the Child-Pugh scale are limited.

Indications:Depression (treatment, prevention of relapse).

Contraindications:

- Hypersensitivity to venlafaxine or another component of the drug;

- simultaneous use with MAO inhibitors;

- severe renal dysfunction (glomerular filtration rate less than 10 ml / min) and / or liver;

- pregnancy;

- the period of breastfeeding;

- age to 18 years.

Carefully:

Recently suffered myocardial infarction, unstable angina, arterial hypertension, tachycardia, history of convulsions, intraocular hypertension, angle-closure glaucoma, manic conditions in the anamnesis,hyponatremia, hypovolemia, dehydration, simultaneous reception of diuretics, suicidal tendencies, predisposition to bleeding from the skin and mucous membranes, renal / hepatic insufficiency.

Pregnancy and lactation:

Do not assign venlafaxine pregnant women and women during breastfeeding due to insufficient data from adequately conducted controlled clinical trials on a sufficiently large sample of such patients. Insufficiently studied the effect of venlafaxine on the mother, fetus or child. Women of childbearing age should be warned about this before starting treatment. In case of pregnancy or planning of pregnancy during the treatment with the drug, you should immediately consult a doctor. Venlafaxine and its metabolite (EFA) penetrate into breast milk. If you need to take the drug, breastfeeding should be discontinued.

In practice, there are cases of venlafaxine administered to mothers during pregnancy and shortly before birth, when in a particular situation the expected benefit to the mother exceeds the potential risk to the fetus.In these cases, neonates often experienced complications that required such measures as increased hospitalization, respiratory support and probing. Complications can develop immediately after birth and are also characteristic in the case of taking other antidepressants from the SSRIs or SSRIs. In such cases, the following clinical symptoms were reported in neonates: external respiratory disorders, cyanosis, apnea, convulsions, temperature instability, feeding difficulties, vomiting, hypoglycemia, muscle hypertension or hypotension, hyperreflexia, tremor, tremor, irritability, lethargy, constant crying, drowsiness or insomnia. Such violations may indicate serotonergic effects of venlafaxine. If venlafaxine was used during pregnancy and the mother's treatment was completed shortly before the birth, a newborn can have withdrawal symptoms. Such a newborn should be excluded from the presence of serotonin syndrome or malignant neuroleptic syndrome. Epidemiological evidence suggests that the use of SSRIs during pregnancy, especially late in pregnancy,may increase the risk of persistent pulmonary hypertension in newborns.

Dosing and Administration:

The drug Venzuert taken with food, preferably at the same time, without chewing and washing down with liquid.

The recommended initial dose is 75 mg in two divided doses daily (37.5 mg twice a day). Depending on the tolerability and effectiveness, the dose can be gradually increased to 150 mg / day. If necessary, increase the dose to 225 mg / day. An increase in the dose of 75 mg / day can be done at intervals of 2 weeks or more, in case of clinical necessity, due to the severity of the symptoms, the dose may be increased in a shorter time, but not less than 4 days. Higher doses (up to a maximum daily dose of 375 mg / day in 2-3 sessions) require inpatient monitoring of patients. After achieving the necessary therapeutic effect, the daily dose can be gradually reduced to a minimum effective level.

Supportive therapy and prevention of relapses

Supportive treatment can last 6 months or more. The minimum effective doses used in the treatment of a depressive episode are prescribed.

Renal insufficiency

With mild renal failure (glomerular filtration rate (GFR) of more than 30 ml / min) correction of the dosing regimen is not required. With moderate renal failure (GFR 10-30 ml / min), the dose should be reduced by 25-50%. In connection with the lengthening of the half-life of venlafaxine and its active metabolite (EFA), such patients should take the entire dose once a day.

It is not recommended to apply venlafaxine with severe renal failure (GFR less than 10 ml / min) due to the lack of experience in this group of patients.

In hemodialysis, the daily dose should be reduced by 50%, the drug should be taken after the end of the hemodialysis session.

Liver failure

With mild hepatic insufficiency (prothrombin time (PV) less than 14 s), correction of the dosing regimen is not required. With moderate hepatic insufficiency (IV 14 to 18 sec), the daily dose should be reduced by 50% or more. It is not recommended to apply venlafaxine with severe hepatic failure due to the lack of experience in this group of patients.

Elderly patients

The elderly patient's age in the absence of any acute and chronic diseases does not require a dose change,However, as with the appointment of other drugs, caution is required in the treatment of elderly patients. Elderly patients should be given the lowest effective dose. When the dose is raised, the patient should be under careful medical supervision.

Abolition of the drug

Stop taking the drug should be done gradually to reduce to a minimum, the risk associated with the cancellation of the drug. At the course of treatment for 6 weeks or more, the period of gradual withdrawal of the drug should be at least 2 weeks and depends on the dose, duration of therapy and individual characteristics of the patient.

Side effects:

Side effects are given in accordance with the classification of the World Health Organization (WHO): very often (≥1 / 10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10000 to <1/1000), very rarely (<1/10000), the frequency is unknown (there is currently no data on the prevalence of adverse reactions).

Common violations: often - weakness, increased fatigue, chills; infrequently - Quincke's edema, photosensitivity reaction; frequency unknown - anaphylactic reactions.

Impaired nervous system: very often - dry mouth, headache; often - unusual dreams, decreased libido, dizziness, insomnia, increased excitability, paresthesia, stupor, confusion, depersonalization, increased muscle tone, tremor; infrequently - apathy, agitation, hallucinations, myoclonus, impaired coordination of movements and balance; rarely - akathisia, psychomotor agitation, epileptic seizures, manic reactions; frequency not established - dizziness, malignant neuroleptic syndrome (ZNC), serotonin syndrome, delirium, extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, suicidal thoughts and behavior, aggression.

Disorders from the gastrointestinal tract: very often - nausea; often - decreased appetite (anorexia), constipation, vomiting; infrequently - bruxism, diarrhea; rarely - hepatitis; frequency not established - pancreatitis.

Disturbances from the respiratory organs: often - yawning, bronchitis, dyspnea; rarely - interstitial lung diseases, eosinophilic pneumonia, chest pain.

Disorders from the cardiovascular system: often - arterial hypertension,hyperemia of the skin; infrequently - postural hypotension, tachycardia, fainting; frequency is unknown - hypotension, lengthening interval QT, ventricular fibrillation, ventricular tachycardia (including bidirectional tachycardia).

Disturbances from the hematopoiesis system: infrequently - hemorrhages in the skin (ecchymosis), gastrointestinal bleeding; frequency unknown - hemorrhages in the mucous membranes, prolonged bleeding time, thrombocytopenia, pathological changes in blood (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia).

Disorders from the metabolism: often - increased serum cholesterol levels, weight loss; infrequently - weight gain; very rarely - an increase in prolactin; frequency unknown - changes in laboratory liver function tests, hepatitis, hyponatremia, syndrome of insufficient secretion of antidiuretic hormone.

From the genitourinary system: often - violations of ejaculation / orgasm (in men), erectile dysfunction (impotence), anorgasmia, dysuric disorders (mainly - difficulty early urination), pollakiuria, menstruation disorders associated with increased bleeding or increased irregular bleeding (menorrhagia.metrorrhagia); infrequently - violations of orgasm (in women), retention of urine; rarely - urinary incontinence.

Impaired sensory organs: often - disorders of accommodation, mydriasis, impaired vision; infrequent - a violation of taste, noise or ringing in the ears; frequency unknown - angle-closure glaucoma.

Diseases from the skin: very often sweating; infrequently - alopecia, fast-passing rash; frequency unknown - erythema multiforme, toxic epidermal necrolysis. Stevens-Johnson syndrome, itching, hives.

Disorders from the musculoskeletal system: frequency is unknown - rhabdomyolysis.

If you stop taking venlafaxine, abruptly cancel or reduce the dose, you may experience symptoms that refer to the so-called withdrawal syndrome: fatigue, asthenia, headache, dizziness, sleep disturbances (drowsiness or insomnia, difficulty falling asleep, unusual dreams), hypomania, anxiety, agitation (increased nervous excitability and irritability), confusion, paresthesia (spontaneously arising unpleasant sensation of numbness, tingling, burning,crawling, etc.), increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are mild and do not require treatment).

Overdose:

Symptoms

Disturbance of consciousness (from drowsiness to coma), agitation, possible vomiting, diarrhea; tremor, decrease or (weak) increase in arterial pressure, dizziness, mydriasis. convulsive conditions, sinus or ventricular tachycardia or bradycardia: changes in the ECG (lengthening interval QT, bundle branch blockade, expansion of the complex QRS).

Postmarketing experience of application indicates that the most frequent overdose of venlafaxine occurred with simultaneous intake of alcohol and / or with other psychotropic drugs. There are repeated reports of deaths. An analysis of the published literature on retrospective studies of venlafaxine overdoses suggests an increased risk of fatal outcomes with venlafaxine when compared with the antidepressant medications available in the SSRI group, but this risk is lower than with tricyclic antidepressants.Epidemiological studies have shown that patients undergoing venlafaxine treatment have a greater burden of suicide risk compared to those taking other SSRIs. However, it remains unclear to what extent such a high proportion of deaths due to an overdose of venlafaxine is due to the toxic properties of the drug itself or the specific characteristics of the group of patients taking venlafaxine. Based on clinical experience, it is recommended in recipes for venlafaxine write out the minimum possible amount of the drug, sufficient only until the next visit of the patient, in order to reduce the risk of intentional overdose (see also section "Special instructions").

Treatment

Symptomatic and supportive therapy is performed. Specific antidotes are unknown. It is recommended continuous monitoring of vital functions (breathing, circulation and heart rhythm). When an overdose is recommended, immediate gastric lavage, taking activated charcoal to reduce absorption of the drug. It is not recommended to induce vomiting at risk of aspiration of vomit.Forced diuresis, dialysis, blood transfusion are ineffective.

Interaction:

Venlafaxine poorly binds to blood plasma proteins and practically does not increase the concentration of concomitant medications, which are characterized by a high association with plasma proteins.

Clinically significant interaction with antihypertensive drugs (many pharmacological groups, including beta-blockers, angiotensin-converting enzyme inhibitors and diuretics) and antidiabetic drugs have not been detected.

Caution should be exercised when concomitant administration with other drugs affecting the central nervous system (CNS), since combinations of venlafaxine with such drugs are not fully understood.

Inhibitors of monoamine oxidase (MAO)

The simultaneous use of venlafaxine with MAO inhibitors, as well as within 14 days after their cancellation, is contraindicated because of the high probability of developing severe side effects up to a lethal outcome). Therapy with MAO inhibitors can be prescribed not less than 7 days after the cancellation of venlafaxine. The use of venflaxin should be discontinued at least 7 days before initiation of reversibleselective MAO inhibitors (moclobemide).

Weakly reversible and non-selective MAO inhibitor linezolid (antimicrobial drugs) and methylene blue (intravenous dosage form) are also not recommended for simultaneous use with venlafaxine.

Serotonergic agents

It should be used with caution at the same time drugs that affect the serotonin system of mediators, such as triptans (sumatriptan, zolmitriptan and others), selective serotonin reuptake inhibitors (SSRIs) and SSRIs (prolonged seizures were noted), tricyclic antidepressants, lithium, sibutramine or fentanyl (and its analogues dextromethorphan, tramadol and others), as well as an excess of tryptophan sources due to the increased potential risk of the occurrence of serotonin syndrome.

Alcohol

During treatment with venlafaxine, alcohol should be completely ruled out. Alcohol enhances the disturbances of psychomotor functions that can cause venlafaxine.

Lithium

Lithium preparations have no significant effect on the pharmacokinetics of venlafaxine.

Diazepam

There was no effect of orally administered diazepam on the pharmacokineticsvenlafaxine and EFA, and, conversely, venlafaxine did not alter the pharmacokinetics of diazepam and its metabolite desmethyldiazepam. In addition, the use of both these drugs does not impair the psychomotor and psychometric effects caused by diazepam.

Cimetidine

Simultaneous use of cimetidine and venlafaxine causes a delay in metabolism during the "first passage" of venlafaxine. The venlafaxine clearance for oral administration decreased by 43%, and the area under the pharmacokinetic curve (AUC) and the maximum concentration (C_mOh) of this drug increased by 60%. However, no such impact has been identified with respect to EFA. Since the total venlafaxine and EFA activity will only increase to a small extent, a dose adjustment for most patients will not be required. However, patients with hypertension, elderly patients and patients with impaired liver or kidney function should consider adjusting the dose of venlafaxine.

Haloperidol

In a study of venlafaxine at an equilibrium concentration at a dose of 150 mg / day, total clearance of oral haloperidol was reduced by 42% after a dose of 2 mg orally.The area under the pharmacokinetic curve (AUC) increased by 70%, and C_mOh increased by 88%, while the half-life of haloperidol (T_1/2) did not change. This should be considered for the correct choice of a dose of haloperidol.

Imipramine

Venlafaxine does not impair the pharmacokinetics of imipramine and 2-hydroxyimipramine. but AUC, FROM_mOh and C_min desipramine (active metabolite imipramine) increased by approximately 35% with concurrent administration of venlafaxine. It also rises from 2.5 to 4.5 times (depending on the dose of venlafaxine: 37.5 mg for 12 hours or 75 mg for 12 hours) concentration of 2-hydroxydesipramine, but the clinical significance of this fact is not known.

Metoprolol

With the simultaneous use of metoprolol and venlafaxine, care should be taken, because of the pharmacokinetic interaction, the concentration of metoprolol in the blood plasma increases by about 30-40%, without changing the concentration of its active metabolite a-hydroxymethoprolol. The clinical significance of this interaction has not been studied. Metoprolol does not affect AUC venlafaxine and EFA.

Risperidone

With simultaneous application with risperidone (despite the increase AUC risperidone) the pharmacokinetics of a pair of active molecules (risperidone and 9-hydroxyrisperidone) does not change significantly when combined with venlafaxine.

Clozapine

During the post-marketing study of venlafaxine, it was found that with simultaneous use with clozapine, its concentration in the blood plasma increases. This was manifested by an increase in the side effects of clozapine, especially with respect to the incidence of seizures.

Indinavir

With simultaneous use, the pharmacokinetics of indinavir (AUC decreases by 28%, and C_mOh decreases by 36%). In venlafaxine, there is no change in pharmacokinetics. The clinical significance of this fact is unknown.

Ketoconazole

A study of pharmacokinetics in combination with ketoconazole showed an increase in plasma concentrations of venlafaxine and EFA in subjects in whom the initial metabolism involving isoenzyme CYP2D6 is both good (X-Met) and bad (P-Met). In particular, C_mOh venlafaxine increased by 26% in X-Meth and by 48% in P-Meth. The values of C_mOh EFA increased by 14% and 29%% in subjects X-Met and P-Met, respectively. AUC venlafaxine increased by 21% in X-Meth and by 70% in P-Meth.Values AUC EFA increased by 23% and 33% in subjects X-Met and P-Meth, respectively.

Facilities, Effects on blood clotting and platelet function (NSAIDs), preparations of acetylsalicylic acid and other anticoagulants)

Serotonin, released by platelets, plays an important role in hemostasis (stopping bleeding). Epidemiological studies demonstrate the relationship between the intake of psychotropic drugs that interfere with the reuptake of serotonin, and the frequency of bleeding in the upper sections of the gastrointestinal tract. This relationship is enhanced if non-steroidal anti-inflammatory drugs (NSAIDs), drugs with acetylsalicylic acid or other anticoagulants are used simultaneously. The increased risk of bleeding in the use of SSRIs and SSRIs (including venlafaxine) concomitantly with warfarin.

Patients receiving warfarin, should be carefully monitored for prothrombin time and / or partial thromboplastin time, especially at the beginning or end of concomitant use with venlafaxine.

Interaction with drugs metabolized by cytochrome P450 isoenzymes

The main ways of metabolism of venlafaxine include isozymes CYP2D6 and CYP3A4: The first one turns venlafaxine in its active metabolite EFA, and the second is less important in the metabolism of venlafaxine compared with CYP2D6 and forms N-desmethylvenlafaxine with little pharmacological activity. Preclinical studies and subsequent clinical data have shown that venlafaxine is a relatively weak inhibitor of CYP2D6. Therefore, even with simultaneous use with medications that moderately suppress the activity of this enzyme (see the example with imipramine above), or in case of genetically determined decrease in the function of CYP2D6, correction of venlafaxine dose is not required, since the total concentration of the active substance and the active metabolite (venlafaxine and EFA) does not change significantly. This positively characterizes venlafaxine when compared with other antidepressants.

Caution should be exercised when concomitant administration with such inhibitors of CYP2D6 as quinidine, paroxetine, fluoxetine. haloperidol, perphenazine, levomepromazine, since in this case venlafaxine can increase the plasma concentration of these substrates CYP2D6.In combination with drugs that inhibit both enzymes (CYP2D6 and CYP3A4), special care must be taken. Such drug interactions have not yet been adequately studied and combinations with such drugs are not recommended.

Venlafaxine does not inhibit the activity of the enzymes CYP3A4, CYP1A2 and CYP2C9, so with drugs such as alprazolam, caffeine, carbamazepine, diazepam, tolbutamide, terfenadine no significant interaction is observed.

Interaction with ketoconazole is described above.

A similar effect can be exerted by such inhibitors of CYP3A3 / 4 as itraconazole, ritonavir.

Other interactions with various concomitant therapeutic factors and food

Against the background of venlafaxine use, special care should be taken with electroconvulsive therapy, since there is no experience with venlafaxine in these conditions.

Significant influence of different types of food on the absorption of venlafaxine and its subsequent transformation into EFA was not revealed. Food (usually high in protein, for example: hard cheeses, fish caviar, turkey), as well as food supplements and fitness rations, which are an increased source of tryptophan,potentially contributes to a greater production of serotonin in the body, which may increase the side effects of serotonergic effects of venlafaxine.

Unwanted pharmacodynamic interaction may occur when taking venlafaxine concomitantly with a medicinal plant, St. John's wort (grass or preparations from it), so this combination is not recommended.

There are reports of false positive results of an immunochromatographic urine test (test strip) test on phencyclidine and amphetamines in patients taking venlafaxine, and even a few days after the withdrawal of venlafaxine. This can be explained by the lack of specificity of this test. Differentiate venlafaxine from phencyclidine and amphetamines can only confirm the test in a specialized anti-doping laboratory.

According to the data available to date, venlafaxine has not proved to be a drug that induces drug abuse or addiction (both in the pre-clinical study of affinity for receptors and in clinical practice).

Special instructions:

Suicide and suicidal behavior

Depression is associated with an increased risk of suicidal thoughts, self-injury and suicide (suicidal behavior). This risk persists until the onset of severe remission. Since there may be no improvement during the first few weeks of therapy or even a longer period of time, careful monitoring of patients is necessary before such an improvement. According to the accumulated clinical experience, the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide attempts or with a high level of suicidal thinking prior to treatment are more likely to be at risk of suicidal thoughts or suicide attempts, such patients need to be closely monitored.

A meta-analysis of placebo-controlled clinical trials of antidepressants with adult patients with mental disorders showed that the risk of suicidal behavior was elevated when taking antidepressants compared with placebo in patients younger than 25 years of age. Medical treatment of these patients and, in particular,of patients with a high risk of suicide should be accompanied by careful monitoring, especially at an early stage of therapy and with dose adjustment. Patients (and caregivers) should be warned about the need to monitor any manifestations of clinical impairment, suicidal behavior or thoughts, and unusual behavioral changes, and seek medical help immediately if these symptoms appear.

A small number of patients taking antidepressants, including venlafaxine, during the start of treatment, changing the dose or discontinuing treatment, aggression may occur.

Clinical studies conducted to date have not revealed a tolerance to or dependence on venlafaxine. Despite this, as with other medications acting on the central nervous system, the physician should establish close monitoring of patients to identify signs of drug abuse, as well as patients with a history of such symptoms.

Special patient groups

Venlafaxine is not approved for use in children.

In patients with previously observed aggression venlafaxine should be used with caution.

In patients with affective disorders, bipolar disorder in the treatment of antidepressants, including venlafaxine, hypomanic and manic conditions may occur.

Like other antidepressants, venlafaxine must be administered with caution to a patient with a history of mania. Such patients need medical supervision.

With venlafaxine therapy, convulsive disorders can occur. Like all antidepressants, venlafaxine should be used with caution in patients with convulsive disorders in the anamnesis, such patients need to be carefully monitored. Treatment should be stopped with the development of seizures.

Akathisia

The use of venlafaxine was associated with the development of akathisia, which is characterized by a feeling of internal motor anxiety that is unpleasant to the patient and manifests itself in the inability of the patient to sit quietly in one position for a long time or remain without movement for a long time. This condition can be observed at the beginning of treatment and during the first weeks of treatment. In patients who develop such symptoms, an increase in dose is not recommended.

Bipolar disorder

Before starting treatment, it is necessary to identify those patients who are at risk for bipolar disorder. Such a check should include a detailed examination of the history, including family history, for the detection of cases of suicide and bipolar disorder. It should be noted that venlafaxine It is not recommended for use in the treatment of bipolar depression.

Use in patients with concomitant diseases

The clinical experience of venlafaxine in patients with concomitant diseases is limited.

It should be used with caution in patients with those diseases in which the effect of venlafaxine on hemodynamic parameters and / or metabolism may be significant.

Patients should be warned about immediate medical attention when rashes, urticaria, or other allergic reactions occur.

Some patients with venlafaxine received a dose-related increase in blood pressure and / or an increased heart rate, so regular monitoring of blood pressure and ECG is recommended, especially during the time of clarification or increase in the dosage of venlafaxine.

In the experience of post-marketing application of venlafaxine (with an overdose), lethal cardiac arrhythmias were recorded. Before the appointment of venlafaxine to patients with a high risk of developing serious cardiac arrhythmias, the ratio of the likely benefit to the possible risk in use should be assessed.

Patients, especially the elderly, should be warned about the possibility of dizziness and imbalance in order to prevent injuries.

When receiving venlafaxine, especially in conditions of dehydration or a decrease in the volume of circulating blood (including elderly patients and patients taking diuretics), hyponatremia and / or a syndrome of insufficient secretion of antidiuretic hormone can be observed.

The use of venlafaxine has not been studied in patients who have recently had myocardial infarction and who suffer from decompensated heart failure. Such patients should be administered with caution.

The use of SSRIs or venlafaxine in patients with diabetes mellitus can cause a change in the level of glucose in the blood plasma. It may be necessary to adjust the dose of insulin and / or antidiabetic medications.

During treatment it is recommended to refrain from taking any alcohol-containing drinks.

The safety and efficacy of venlafaxine in combination with drugs that reduce body weight (including phentermine) have not been established. It is not recommended simultaneous reception of venlafaxine and drugs that reduce body weight.

Women of childbearing age should apply appropriate contraceptive methods during venlafaxine intake.

Special symptoms and conditions, the occurrence of which is possible with drug treatment

Dry mouth is noted in 10% of patients who received venlafaxine. This can increase the risk of developing caries. Patients should carefully observe oral hygiene.

The use of venlafaxine can cause the development of akathisia characterized by subjective unpleasant sensations or motor anxiety and the need to move frequently, which is often accompanied by inability to sit or stand still. This mainly occurs during the first few weeks of treatment. Increasing the dose in patients who develop these symptoms can have undesirable consequences.

In placebo-controlled clinical trials, 5.3% of patients had a clinically significant increase in serum cholesterol. It is necessary to control the level of cholesterol in long-term treatment.

The withdrawal syndrome

During the cessation of treatment, withdrawal syndrome is common, especially with a sudden cessation. The risk of withdrawal may depend on several factors, including the duration of treatment, the amount of therapeutic doses and the rate at which they are reduced. Very rarely reported on these symptoms in patients who accidentally missed the next dose of the drug.

Symptoms of withdrawal syndrome usually occur within the first few days after discontinuation of treatment. Usually these symptoms pass for 2 weeks, although in some people they can be 2-3 months or more. It is recommended to gradually reduce the dose of venlafaxine upon discontinuation of the drug for several weeks or months, depending on the severity of the clinical symptoms of the disease.

Serotonin syndrome

Taking venlafaxine, like other serotonergic drugs, can cause a serotonin syndrome, a potentially life-threatening condition,especially with the simultaneous use of other drugs that can affect serotonergic neurotransmitter systems, such as MAO inhibitors (see section "Interactions with other drugs").

Symptoms of serotonin syndrome may include changes in mental status (excitation, hallucinations, coma), autonomic instability (tachycardia, lability of blood pressure, hyperthermia), neuromuscular disorders (hyperreflexia, impaired coordination) and / or gastrointestinal symptoms (nausea, vomiting, diarrhea).

Effect on the ability to drive transp. cf. and fur:During the treatment with venlafaxine, care must be taken when driving vehicles or performing work that requires a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules of prolonged action, 37.5 mg, 75 mg and 150 mg.

Packaging:

Capsules of prolonged action 37.5 mg

For 7 capsules in a blister of PVC / aluminum foil laminated with low density polyethylene. For 2 or 4 blisters together with instructions for use in a cardboard box. 30 capsules in a vial of HDPE.

1 bottle with instructions for use in a cardboard box.

Capsules of prolonged action 75 mg, 150 mg

For 14 capsules in a blister of PVC / aluminum foil laminated with low density polyethylene. For 1 or 2 blisters together with instructions for use in a cardboard box.

30 capsules in a vial of HDPE. 1 bottle with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001017

Date of registration:18.10.2011 / 13.10.2016

Expiration Date:18.10.2016

Date of cancellation:2017-03-23

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp23.03.2017

Illustrated instructions

Instructions

Wensuert (Vensuert)