Venlafaxine Organic - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline - 53.03 mg or 106.06 mg, lactose monohydrate (sugar milk) - 35.10 mg or 70.20 mg, carboxymethyl starch sodium (primogel) - 15.70 mg or 31.40 mg, povidone (low molecular weight polyvinylpyrrolidone medical) K-17 - 2.65 mg or 5.30 mg, magnesium stearate - 1.10 mg or 2.20 mg,

shell: Opapray II (85F28751) white [polyvinyl alcohol - 2.00 mg or 4.00 mg, titanium dioxide 1.25 mg or 2.50 mg, macrogol (polyethylene glycol) 1.01 mg or 2.02 mg, talc 0.74 mg or 1.48 mg] is 5.00 mg or 10.00 mg.

Description:

Round, biconvex tablets, covered with a film coat of white or almost white color. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Venlafaxine - an antidepressant not chemically related to any class of antidepressants (tricyclic, tetracyclic or other), is a racemate of two active enantomers.

Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA), are potent inhibitors of serotonin and noradrenaline reuptake (in abbreviated form: SSRI or SIOZsin) and weak inhibitors of dopamine reuptake.

The mechanism of antidepressant drug effect is associated with its ability to potentiate the transmission of the nerve impulse in the central nervous system (CNS). Venlafacchin and EFA equally affect the re-uptake of the abovementioned neurotransmitters, while they do not have an affinity (studied in vitro) with cholinergic (muscarinic), histamine (H1), alpha1-adrenergic, opioid and benzodiazepine receptors, do not inhibit monoamine oxidase (MAO) activity. Also has no affinity for opiate, phencyclidine or N-methyl-d-aspartate (NMDA) receptors. On the inhibition of serotonin reuptake venlafaxine is inferior to selective serotonin reuptake inhibitors (SSRIs). Besides, venlafaxine and O-desmethylvenlafaxine reduce beta-adrenergic reactivity both after a single administration and at a constant intake.

Pharmacokinetics:

Absorption:

Absorption from the gastrointestinal tract is good, about 92% for a single dose, is not quantitatively dependent on food intake.

Distribution:

The total bioavailability is 40-45%, which is associated with intensive pre-systemic metabolism in the liver. Venlafaxine and EFA bind to human plasma proteins at 27 and 30%, respectively; they both penetrate into breast milk. In the range of daily doses of venlafaxine 75-450 mg itself venlafaxine and EFA have linear kinetics. Time to reach the maximum concentration in the blood plasma (TC_mOh) venlafaxine and EFA - 2 and 3 hours, respectively, after taking venlafaxine tablets inside. In the case of taking long-acting venlafaxine forms, TC_mOh 5.5 and 9 hours respectively.

The half-life (T_1/2) was 5 ± 2 hours and 11 ± 2h, for venlafaxine and EFA, respectively. The equilibrium concentration in plasma (C_ss) for venlafaxine and EFA is achieved after 3 days of repeated intake of therapeutic doses.

Metabolism:

Metabolized mainly in the liver with the participation of isoenzyme CYP2D6 to a single pharmacologically active metabolite (EFA), as well as to an inactive metabolite N-desmethylvenlafaxine. Venlafaxine is a weak isoenzyme inhibitor CYP2D6, does not inhibit CYP1A2, CYP2C9 or CYP3A4.

Excretion:

It is mainly excreted by the kidneys: approximately 87% of the single dose taken is excreted in the urine within 48 hours (5% unchanged, 29% unconjugated EFA, 26% conjugated EFA, 27% other inactive metabolites), and 72 92% of the drug is excreted by the kidneys.

The mean ± standard deviation for plasma clearance of venlafaxine and EFA is 1.3 ± 0.6 and 0.4 ± 0.2 l / h / kg, respectively; the apparent half-life of 5 ± 2 and 11 ± 2 hours,respectively; apparent (in the equilibrium state) volume distribution of 7.5 ± 3.7 and 5.7 ± 1.8 l / kg, respectively.

Special Groups:

Floor and age the patient does not have a significant effect on the pharmacokinetic parameters of venlafaxine and EFA.

For elderly patients a special dose adjustment is not required depending on the age.

In patients with low isoenzyme activity CYP2D6 there is no need to select individual doses. Despite the multidirectional change in concentrations taken separately, namely, venlafaxine (increases) and EFA (decreases), the sum of the areas under the pharmacokinetic curves of these two active substances does not actually change due to a decrease in the isoenzyme activity CYP2D6, accordingly, dose adjustments are not required.

In patients with hepatic and renal insufficiencyfrom medium to severe venlafaxine metabolism and elimination of EFA decreases, C_mOh venlafaxine and EFA, elongated T_1/2. The decrease in the total clearance of venlafaxine is most pronounced in patients with creatinine clearance (KK) kidneys below 30 ml / min, as well as in patients on renal dialysis (T_1/2increases by 180% for venlafaxine and 142% for EFA, and the clearance of both active substances decreases by about 57%). For such patients, especially on hemodialysis, individual selection of venlafaxine dose and control of kinetics are necessary taking into account the duration of treatment with this drug.

Although data for patients with hepatic insufficiency of severe degree on the Child-Pugh scale are limited, it should be taken into account that individual variations in pharmacokinetics, in particular, clearance of the drug and its T_1/2, are of a very diverse nature, which should be taken into account in the appointment of venlafaxine to such patients.

In patients with Child-Pugh class A (mild liver function abnormalities) and Child-Pugh class B (moderate impairment) T_1/2venlafaxine and EFA elongated approximately 2 times compared with healthy patients, and the clearance is reduced by more than half.

Indications:

Depression. Prevention and treatment.

Contraindications:

Hypersensitivity to venlafaxine or to any of the excipients, concomitant use with MAO inhibitors (see also "Interactions with other drugs"), severe renal and / or hepatic impairment (GFR) of less than 10 ml / min) .

The drug is contraindicated at the age of under 18, during pregnancy and lactation.

Carefully:

Recent myocardial infarction, unstable angina, hypertension, tachycardia, convulsions history, increased intraocular pressure, angle-closure glaucoma, manic state history, a predisposition to bleeding from the skin and mucous membranes, initially reduced body weight.

Pregnancy and lactation:

Do not assign venlafaxine pregnant and breastfeeding women; safety of the drug during pregnancy and lactation in women has not been established sufficiently, given that there are no adequately controlled clinical studies on a sufficiently large sample of patients. This applies to the health of both the mother and, to a greater extent, the fetus / child.

Women of childbearing age should be warned about this before treatment, immediately consult a doctor if you become pregnant or planning pregnancy during drug treatment.

Venlafaxine and its metabolite (EFA) are excreted in breast milk. If you need to take the drug during lactation, it is necessary to stop breastfeeding.

In practice, there are cases of venlafaxine administered to mothers during pregnancy and shortly before delivery, 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: an increase in the length of hospitalization, maintenance of breathing and feeding through the probe. These complications can develop immediately after birth and are also characteristic in the case of taking other antidepressants from the group of SSRIs or SSRIs (not containing venlafaxine). 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 the drug 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:

Inside.

A drug Venlafaxine take during meals, preferably at the same time, without chewing and washing down with liquid.

Recommended initial dose is 75 mg in two 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) 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), since there is no reliable data on such therapy. 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) is less than 14 sec) 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 insufficiency, since there is no reliable data on such therapy.

Elderly patients: the elderly age of the patient in the absence of any acute and chronic diseases does not require a dose change, however (as with the appointment of other drugs) in the treatment of elderly patients requires caution. 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

The discontinuation of taking the drug should be carried out gradually, to minimize 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:

Frequency of side effects: 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 not established (there is currently no data on the prevalence of adverse reactions).

General symptoms: often - weakness, increased fatigue, chills; infrequently - Quincke's edema, photosensitivity reaction; frequency not established - anaphylactic reactions.

From the 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 is not established - dizziness, malignant neuroleptic syndrome (CNS), serotonin syndrome, delirium, extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, suicidal thoughts and behavior, aggression.

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

On the part of the respiratory system: often - yawning, bronchitis, dyspnea; rarely: interstitial lung diseases (ESR) and eosinophilic pneumonia, chest pain.

From the side of the cardiovascular system: often - arterial hypertension, hyperemia of the skin; infrequently - postural hypotension, tachycardia, fainting; frequency not established - hypotension, QT interval elongation, ventricular fibrillation, ventricular tachycardia (including bidirectional tachycardia).

On the part of the hematopoiesis system: infrequently - hemorrhages in the skin (ecchymosis), gastrointestinal bleeding; frequency not established - hemorrhages in the mucous membranes, prolonged bleeding time, thrombocytopenia, pathological changes in blood (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia).

From the side of metabolism: often - increased serum cholesterol levels, weight loss; infrequently - weight gain; very rarely - an increase in prolactin; frequency is not established - changes in laboratory tests of liver function, 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 - difficulties at the beginning of 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.

From the sense organs: often - disorders of accommodation, mydriasis, impaired vision; infrequent - a violation of taste, noise or ringing in the ears; frequency not established - angle-closure glaucoma.

From the skin: very often - sweating; infrequently - alopecia, fast-passing rash; frequency is not established - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus, urticaria.

From the side of the musculoskeletal system: frequency not established - rhabdomyolysis.

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

Overdose:

Overdose Symptoms: impaired 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 on the ECG (prolongation of the interval Q-T, blockade of the bundle of the bundle, expansion of the QRS complex).

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.Published literature on retrospective studies of venlafaxine overdoses report that such an increased risk of fatal outcomes may be attributable to venlafaxine when compared with the available antidepressant drugs in the SSRI group, but this risk is lower than the risk inherent in tricyclic antidepressants. Epidemiological studies have shown that those patients treated with venlafaxine have a greater burden of suicide compared to those treated with SSRIs (other than venlafaxine). However, it remains unclear to what extent such high mortality rates (due to venlafaxine overdose) are due to the toxic properties of the drug itself or the specific characteristics of that group of patients treated with venlafaxine. According to clinical experience, it is recommended in prescriptions 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. 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, without having an increased bond with blood plasma proteins, practically does not increase the concentration of concomitant medications, which are characterized by a high bond 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.

Care should be taken when concomitant administration with other drugs affecting the central nervous system (CNS), since combinations of venlafaxine with all such drugs have not been studied.

Inhibitors of monoamine oxidase (MAO)

Contraindicated concomitant use of venlafaxine with MAO inhibitors, as well as within 14 days after their withdrawal (likely the risk of severe adverse effects up to a lethal outcome). Therapy with MAO inhibitors can be prescribed not less than 7 days after discontinuation of the drug Venlafaxine. Administration of the drug Venflaxin should be discontinued at least 7 days before the onset of reversible selective MAO inhibitorsmoclobemide). 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

Caution should be exercised at the simultaneous use of 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 pharmacokinetics of venlafaxine and EFA, and, conversely, venlafaxine did not alter the pharmacokinetics of diazepam and its metabolite desmethyldiazepam. In addition, the appointment of both these drugs does not impair the psychomotor and psychometric effects caused by diazepam.

Cimetidine

Simultaneous administration of cimetidine and venlafaxine was manifested in 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, such an impact did not manifest itself with regard to EFA.Since the total activity of venlafaxine and EFA is expected to increase only to a small extent, dose adjustments for most of the usual patients will not be required. However, patients with existing (identified) hypertension, elderly patients and those who have a violation of the liver or kidney function, it is possible to adjust the dose of venlafaxine.

Haloperidol

In the study, where venlafaxine was prescribed in the stage of equilibrium concentration at a dose of 150 mg / day, there was a decrease in total clearance of oral haloperidol by 42% after a dose of 2 mg orally; the area under the pharmacokinetic curve (AUC) increased by 70%, and FROM_max 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, C_max and C_min desipramine (an active metabolite of 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), the 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 α-hydroxymethoprolol. The clinical significance of this interaction has not been studied. Metoprolol does not affect the venlafaxine AUC 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.

Means that affect blood clotting and platelet function (NSAIDs, acetylsalicylic acid preparations 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 risk of bleeding in the appointment of SSRIs and SSRIs (including venlafaxine) concomitantly with warfarin. Patients assigned warfarin, should be carefully monitored for prothrombin time and / or partial thromboplastin time, especially when the combined use with venlafaxine begins or ends.

Interaction with other drugs at the level of the studied metabolism with 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 a product N-desmethylvenlafaxine with little pharmacological activity. Preclinical studies showed, and then it was clinically confirmed that venlafaxine is a relatively weak inhibitor CYP2D6. Therefore, even when administered with moderately suppressing activity of this enzyme with drugs (see the example with imipramine above), or in patients with genetically determined function decline CYP2D6, dose correction of venlafaxine is not required, since the total concentration of active substance and active metabolite (venlafaxine and EFA) does not change significantly. This positively characterizes venlafaxine when compared with other antidepressants. Care should be taken when concomitant administration with such inhibitors CYP2D6, as quinidine, paroxetine, fluoxetine, haloperidol, perphenazine, levomepromazine, since in this case venlafaxine can potentially 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 been sufficiently investigated, and in this case such a combination of drugs is not recommended.

Also venlafaxine does not suppress enzyme activity CYP3A4, CYP1A2 and CYP2C9, so with such drugs 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 CUR3A3 / 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 dietary supplements and fitness rations that are an increased source of tryptophan, potentially contributes to 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 simultaneously with a medicinal plant, St. John's wort (grass or various preparations from it), 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. Distinguish between 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 meditation on suicidal topics before starting 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. The drug 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 states 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, to identify suicides, 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.

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.

Taking 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.

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

Dry mouth 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 development akathisia, characterized by subjective unpleasant sensations or motor anxiety and the need to move often, 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 reported 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 if it is 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 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 serotonin syndrome, a potentially life-threatening condition, especially when other drugs are used that can affect serotonergic neurotransmitter systems, such as MAO inhibitors (see "Interactions with other medicinal products ").

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 period, care should be taken when performing potentially hazardous jobs requiring increased concentration of attention and speed of the psychomotor reaction (including driving and controlling the mechanisms).

Form release / dosage:Tablets, film-coated, 37.5 mg and 75 mg.

Packaging:

For 10 tablets in a planar cell package.

By 3 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use at the end of the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003713

Date of registration:29.06.2016 / 12.12.2016

Expiration Date:29.06.2021

The owner of the registration certificate:ORGANICS, JSC ORGANICS, JSC Russia

Manufacturer: & nbsp

ORGANICS, JSC Russia

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Venlafaxine Organa (Venlafaxine ORGANICA)