Instruction for use: Venlafaxine 75 mg

International Nonproprietary Name (INN): Venlafaxine

Pharmaceutic group: Antidepressant

Presentation:

Tablets 37.5 mg, 75 mg n30.

Available with prescription

Indications for Venlafaxine

Venlafaxine is indicated for the treatment or prevention of depression. The prescriptions are usually available from a psychiatrist.

Venlafaxine is an orally administered serotonin-norepinephrine reuptake inhibitor (SNRI) class medication with a chemical structure unrelated to that of the known (tricyclic, tetracyclic or other) or other available antidepressant agents. Venlafaxine is available as tablets (usual tablets), containing Venlafaxine HCl (racemic mixture of enantiomers). The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant affinity for muscarinic, histaminergic, or α-1 adrenergic receptors in vitro. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity.

Venlafaxine in the form of usual tablets should be administered, as a rule, twice daily, during the meal, at the equal time points from day to day. Course of treatment is usually rather long, the first signs of depression’s relief show after 1-2 weeks of treatment with the Venlafaxine.

A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.

More information about Venlafaxine’s medical usage you can find in the approved leaflet (in Russian language only), which is included in each carton box of the product.

Trade name of the drug – Venlafaxine

Dosage Form: tablets

Active substance:

venlafaxine hydrochloride - 42.42 mg and 84.84 mg, or 37.5 mg or 75 mg of venlafaxine;

Excipients: microcrystalline cellulose - 67.31 / 134.62 mg, pregelatinised starch - 49.50 / 99.00 mg colloidal silicon dioxide (Aerosil) - 0.82 / 1.64 mg of talc - 3.30 / 6 60 mg of magnesium stearate - 1.65 / 3.30 mg.

Description:

Tablets from white to white with a yellowish shade, allowed light marbling, flat-cylindrical, with a facet.

Pharmacotherapeutic group: Antidepressant

ATX code: N06AX16

Pharmacological Properties of VenlafaxinePharmacodynamics

Venlafaxine - antidepressant that is chemically not related to any class of antidepressants (tricyclic, tetracyclic, or other), it is a racemate of two active enantiomers. Venlafaxine and its main metabolite, O-desmetilvenlafaksin (EFA), are potent inhibitors of the reuptake of serotonin and norepinephrine (in abbreviated form: SNRIs or SIOZSiN) and weak inhibitors of dopamine reuptake. The mechanism of antidepressant action of the drug associated with the ability to enhance the activity of neurotransmitters in the transmission of nerve impulses in the central nervous system (CNS). Venlafaxine and EFA equally effectively affect reuptake aforementioned neurotransmitters, and they do not have an affinity (studied in vitro) cholinergic (muscarinic), histamine (H1), alpha1-adrenergic, opioid and benzodiazepine receptor, do not inhibit the activity of monoamine oxidase (MAO) . By inhibiting serotonin reuptake, venlafaxine inferior selective serotonin reuptake inhibitor (SSRI).

Pharmacokinetics

Absorption:

Absorption from the gastrointestinal tract is good, about 92% for single-dose quantity is independent of food intake.

Distribution:

The total bioavailability - 40-45%, due to the intensive first-pass metabolism in the liver. Venlafaxine and EFA bind to human plasma proteins at 27 and 30%, respectively; they both get into breast milk. The range of daily doses of venlafaxine 75-450 mg of venlafaxine and EFA itself have a linear kinetics. The time to reach maximum plasma concentration (TCmax) venlafaxine and EFA - 2 and 3 h, respectively, after taking the tablets Venlafaxine inside. In case of receiving prolonged forms of venlafaxine indicators TCmax 5,5, and 9 hours, respectively.

The half-life (T1 / 2) was 5 ± 2 hours and 11 ± 2 hours for venlafaxine and EFA sootvetstvenno.Ravnovesnaya plasma concentration (Css) for venlafaxine and EFA is reached after 3 days of multiple therapeutic doses.

Metabolism:

Metabolized mainly in the liver with CYP2D6 isozyme to a single pharmacologically active metabolite (EFA) and to an inactive metabolite N-desmetilvenlafaksina. Venlafaxine is a weak inhibitor of isozyme CYP2D6, did not inhibit CYP1A2, CYP2C9 or CYP3A4.

Excretion:

Report mostly kidneys: approximately 87% received a single dose is excreted in the urine within 48 hours (5% in unchanged form, 29% in the form of unconjugated EFA, 26% in the form of conjugated EFA, 27% of other inactive metabolites), and in 72 h kidneys derived 92% of the drug.

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

Special groups

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

For elderly patients special dose adjustments depending on the age is required.

In patients with low CYP2D6 isozyme activity is not necessary in the selection of individual doses. Although concentrations opposite changes taken separately, namely venlafaxine (improved) and EFA (reduced), sum of the areas under the curve of these two active substances actually changes due to decreased activity of the isoenzyme CYP2D6, respectively dose adjustment is required.

Patients with hepatic and renal insufficiency of moderate to severe venlafaxine metabolism and excretion of the EFA reduced Cmax increased venlafaxine and EFA, lengthens T1 / 2. Reducing the total clearance of venlafaxine is most pronounced in patients with creatinine clearance (CC) by the kidneys below 30 ml / min and in patients who are on kidney dialysis (T1 / 2 increased by 180% for venlafaxine and 142% for EFA, and the clearance of both active substances is reduced by about 57%). For such patients, especially those on hemodialysis, individual selection of doses of venlafaxine and control the kinetics taking into account the duration of treatment with this drug.

Although the data for patients with severe hepatic insufficiency degree in Child-Pugh limited, it should be noted that individual variations in pharmacokinetics, in particular, the clearance of the drug and its T1 / 2, are very diverse in nature, which should be taken into account in the appointment of venlafaxine in these patients.

In patients with class A according to Child-Pugh (light abnormal liver function) and Class B Child-Pugh (Middle violations) T1 / 2 of venlafaxine and EFA extended approximately 2-fold compared with healthy patients and clearance decreased by more than half .

Indications for Venlafaxine

Depression. Prevention and treatment.

Contraindications forVenlafaxine

Hypersensitivity to venlafaxine or to any of the excipients, the simultaneous application with MAO inhibitors (see. Also section "Interaction with other medicinal products") severe renal dysfunction and / or hepatic impairment (glomerular filtration rate (GFR) of less than 10 ml / min) .

Acceptance of the drug is contraindicated under the age of 18 years, during pregnancy and lactation.

Precautions: Recent myocardial infarction, unstable angina, hypertension, arrhythmias (especially tachycardia), convulsions in history, increased intraocular pressure, angle-closure glaucoma, manic state in history, suicidal tendencies, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight, hyponatraemia, dehydration, simultaneously with diuretics or drugs (drugs) used for the treatment of obesity (see. also "Special instructions" section).

Pregnancy and lactation

You should not assign venlafaxine pregnant and lactating women, as 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 mother and, to a greater extent the fetus / baby. 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 allocated into breast milk. If you want to receive the drug during lactation is necessary cessation of breastfeeding.

In practice, cases of appointment of venlafaxine found the mother during pregnancy and just before delivery, when in a specific situation the expected benefit to the mother outweighs the potential risk to the fetus. In these cases, the infants were frequently observed complications that require: increased length of hospitalization, respiratory support, and tube feeding. These complications can develop immediately after birth and is characterized in the case of receiving other antidepressants of the SSRI or SNRI groups (not containing venlafaxine). In such cases, it reported the following clinical symptoms in the newborn: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, muscle hypertonia or hypotonia, hyperreflexia, tremor, trembling, irritability, lethargy, constant crying, somnolence or insomnia. Such violations may indicate serotonergic effects of the drug venlafaxine. If venlafaxine used during pregnancy, and maternal treatment was completed shortly before the birth, the newborn may have withdrawal symptoms. Such a newborn should exclude the presence of serotonin syndrome or neuroleptic malignant syndrome. Epidemiological evidence suggests that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension of newborns.

Venlafaxine Dosage and Administration

Inside.

The drug is venlafaxine taken with food, preferably at the same time, liquid squeezed liquid. The recommended starting dose is 75 mg daily in two stages (at 37.5 mg 2 times a day). Depending on tolerability and efficacy, the dose can be gradually increased up to 150 mg / day. If necessary, increase the dose to 225 mg / day. Increasing the dose to 75 mg / day can be made at intervals of 2 weeks or more, in case of clinical necessity, due to the severity of 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 hours) patients require inpatient observation. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

Supportive therapy and relapse prevention: supportive treatment may continue for 6 months or more. Appointed by the minimum effective dose used in the treatment of depressive episodes.

Renal failure: for mild renal insufficiency (glomerular filtration rate (GFR) was 30 mL / min) correction mode is not required. At moderate renal failure (GFR 10-30 ml / min), the dose should be reduced by 25-50%. In connection with the elongation of the half-life of venlafaxine and its active metabolite (EFA), such patients should take the entire dose once a day. Venlafaxine is not recommended in severe renal failure (GFR of less than 10 ml / min) as valid data are no such therapy. In hemodialysis the daily dose should be reduced by 50%, to take the drug should be after the end of hemodialysis.

Hepatic impairment: in mild hepatic insufficiency (prothrombin time (PT) of less than 14 seconds) correction mode is not required. In moderate hepatic insufficiency (PV from 14 to 18 seconds) daily dose should be reduced by 50% or more. Not recommended for venlafaxine in severe hepatic insufficiency, since reliable data on such therapy available.

Elderly patients: patient's advanced age without any acute and chronic diseases requires no change in dose, however, (as in the assignment of other drugs) need to be careful in the treatment of elderly patients. Elderly patients should use the lowest effective dose. When the dose the patient should be under close medical supervision.

Cancel the drug

Discontinuation of the drug should be gradual, in order to minimize the risk associated with the abolition of the drug. In the course of treatment for 6 weeks or more during the gradual withdrawal of the drug should be at least 2 weeks and depends on the dose, duration of therapy and individual patient characteristics.

Side effect ofVenlafaxine

The frequency of side effects: very common (≥ 1/10), often (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rarely (≥ 1/10000 to <1/1000 ), very rare (<1/10000), the frequency is not set (the currently available data on the incidence of adverse reactions are absent).

Common symptoms: often - weakness, fatigue, chills; seldom - angioedema, photosensitivity reactions; the frequency has not been established - anaphylactic reactions.

From the nervous system: very often - dry mouth, headache; often - abnormal dreams, decreased libido, dizziness, insomnia, irritability, paresthesias, stupor, confusion, depersonalization, increased muscle tone, tremors; infrequently - apathy, agitation, hallucinations, myoclonus, impaired coordination of movement and balance; rarely - akathisia, agitation, seizures, manic reaction; the frequency has not been established - vertigo, neuroleptic malignant syndrome (NMS), serotonin syndrome, delirium, extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, suicidal ideation and behavior, aggression.

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

From the respiratory system: often - yawning, bronchitis, shortness of breath; Rare: interstitial lung disease (ILD), and eosinophilic pneumonia, chest pain.

Since the cardiovascular system: often - arterial hypertension, flushing of the skin; infrequently - postural hypotension, tachycardia, syncope; the frequency has not been established - hypotension, prolongation of the interval QT, ventricular fibrillation, ventricular tachycardia (including bidirectional tachycardia).

Hematopoietic system: rarely - bleeding in the skin (ecchymosis), gastrointestinal bleeding; the frequency has not been established - bleeding in the mucous membranes, prolonged bleeding time, thrombocytopenia, blood dyscrasias (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia).

On the part of metabolism: often - increase the level of cholesterol in the blood serum, weight loss; Infrequent - increased body mass index; very rare - increase in prolactin; the frequency has not been established - a change of laboratory samples of the liver, hepatitis, hyponatremia, syndrome of inadequate secretion of antidiuretic hormone.

With the genitourinary system: often - abnormal ejaculation / orgasm (males), erectile dysfunction (impotence), anorgasmia, dizuricheskie disorders (mainly - difficulties at the beginning of urination), pollakiuria, violation of menstruation associated with increased bleeding or increased irregular bleeding ( menorrhagia, metrorrhagia); rarely - a violation of orgasm (for women), urinary retention; rare - incontinence.

From the senses: common - accommodation disturbances, mydriasis, blurred vision; seldom - taste disturbance, noise or ringing in the ears; the frequency has not been established - closure glaucoma.

For the skin: very often - sweating; rare - alopecia, a transient rash; the frequency has not been established - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus, urticaria.

From the musculoskeletal system: the frequency has not been established -rabdomioliz.

If discontinuation of venlafaxine, abrupt cancellation or reduction of the dose may experience symptoms that relate to the so-called withdrawal syndrome: fatigue, asthenia, headache, dizziness, sleep disturbances (drowsiness or insomnia, difficulty falling asleep, the appearance of unusual dreams), hypomania, anxiety, agitation (increased nervous irritability and irritability), confusion, paraesthesia (spontaneously arising unpleasant feeling of numbness, tingling, burning, pins and needles, etc.), increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are slightly pronounced and do not require treatment).

overdose

Overdose symptoms: disturbance of consciousness (from somnolence to coma), agitation, possible vomiting, diarrhea; tremors, decreased or (slight) increase in blood pressure, dizziness, mydriasis, convulsive state, sinus or ventricular tachycardia or bradycardia; ECG changes (prolongation of the interval Q-T, bundle branch block, the expansion of the QRS complex).

Post-marketing experience in the application indicates that the most frequently venlafaxine overdose occurred at simultaneous reception of alcohol and / or other psychotropic drugs. There are numerous reports of deaths.

Published sources for retrospective studies of venlafaxine overdose reported that this increased risk of fatal outcomes can be inherent in it venlafaxine when comparing it with the existing medical reverse SSRI antidepressants, but this risk is lower than the risk inherent tricyclic antidepressants. Epidemiological studies have shown that those patients who are treated with venlafaxine, have a greater burden in the respect of the risk of committing suicide compared to those patients who are treated with SSRIs (other than venlafaxine). However, until now it remained unclear to what extent such a high percentage of deaths (due to an overdose of venlafaxine) are due to the toxic properties of the drug or the special characteristics of that group of patients treated with venlafaxine. According to clinical experience, it is recommended in recipes on venlafaxine prescribe the lowest possible amount of drug sufficient only until the next visit of the patient, in order to reduce the risk of intentional overdose (see. Also "Special Instructions" section).

Treatment: symptomatic and supportive therapy. Specific antidotes are not known. Recommended continuous monitoring of vital functions (breathing, blood circulation and heart rhythm). In case of overdose recommended immediate gastric lavage, administration of activated charcoal to reduce absorption of the drug. Do not induce vomiting at risk of aspiration. Forced diuresis, dialysis, blood transfusions are ineffective.

Interaction

The risk of myopathy during treatment with other drugs of this class is increased by the simultaneous Venlafaxine, itself not having increased bond to plasma proteins, almost at the same time increases the concentration of the medication, which are characterized by high bond to plasma proteins. No clinically significant interaction with antihypertensive (many pharmacological groups, including beta-blockers, angiotensin-converting enzyme inhibitors and diuretics) and antidiabetic agents has been detected. Caution should be exercised with concomitant administration with other drugs that affect the central nervous system (CNS), as the combination of venlafaxine with all such drugs have not been studied.

monoamine oxidase inhibitors (MAOIs)

Concomitant use of venlafaxine with MAO inhibitors, as well as for 14 days after their cancellation (probable risk of severe side effects, including death). MAO inhibitor therapy can be given not less than 7 days after discontinuation of the drug venlafaxine. Admission Venflaksin the drug should be discontinued at least 7 days prior to receiving the reversible selective MAO inhibitors (moclobemide). Mild reversible and non-selective inhibitor MAOlinezolid (antimicrobial drugs) and methylene blue (intravenous formulation) is also not recommended for simultaneous use with venlafaxine.

serotonergic agents

Should be wary of the simultaneous use of drugs that affect the serotonin neurotransmitters systems, such as triptans (sumatriptan, zolmitriptan, and others.), Selective serotonin reuptake inhibitors (SSRIs) and SNRIs (observed prolonged seizures), tricyclic antidepressants, lithium, fentanyl or sibutramine (dextromethorphan and its analogs, and tramadol al.) and an excess of tryptophan source potential due to increased risk for serotonin syndrome.

Alcohol

During treatment with venlafaxine should completely eliminate alcohol. Alcohol enhances psychomotor disturbances that may cause venlafaxine.

Lithium

Lithium drugs do not significantly affect the pharmacokinetics of venlafaxine.

Diazepam

There were no effect of oral administration of diazepam on the pharmacokinetics of venlafaxine and EFA, and, conversely, venlafaxine did not alter the pharmacokinetics of diazepam and its metabolite desmetildiazepama. Moreover, the purpose of both of these drugs does not impair psychomotor and psychometric effects induced by diazepam.

cimetidine

Co-administration of cimetidine and venlafaxine showed in the metabolism of delay in "the first passage" venlafaxine. Clearance of venlafaxine at intake decreased by 43% and the area under the curve (AUC) and maximum concentration (Cmax) of the drug have increased by 60%. However, such effects are not evident in EFA. Since the overall activity of venlafaxine and EFA is expected to increase with only a small degree, the dose adjustment for patients most usual is required. However, patients with existing (identified) hypertension, elderly patients and those who have a liver or renal function, a dose adjustment of venlafaxine is possible.

Haloperidol

In a study where venlafaxine was administered at the stage of equilibrium concentration at a dose of 150 mg / day, there was a decrease in total oral clearance of haloperidol by 42% after a dose of 2 mg orally; wherein the area under the concentration-time curve (AUC) increased by 70%, and Cmax increased by 88%, while the half-life of haloperidol (T 1/2) is not changed. This should be considered for a correct choice of the dose of haloperidol.

imipramine

It does not degrade the pharmacokinetics of venlafaxine and imipramine gidroksiimipramina 2. However, AUC, Cmax and Cmindesipramina (the active metabolite of imipramine) increased by approximately 35% while receiving venlafaxine. Also increases from 2.5 to 4.5 times (depending on the dose of venlafaxine 37.5 mg per 12 hours, or 75 mg per 12 hours) 2 gidroksidesipramina concentration, but the clinical significance of this fact is not known.

metoprolol

With simultaneous use of metoprolol and venlafaxine should be careful, as a result of a pharmacokinetic interaction between metoprolol plasma concentration is increased by about 30-40%, with no change in the concentration of its active metabolite, α-gidroksimetoprolola. The clinical significance of this interaction has not been investigated. Metoprolol not affect the AUC of venlafaxine and EFA.

Risperidone

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

Clozapine

During post-marketing study of venlafaxine revealed that while the use of clozapine concentration in plasma increases. This was manifested increased side effects of clozapine, especially regarding the frequency of seizures.

indinavir

In an application changes the pharmacokinetics of indinavir (AUC decreased by 28% and Cmax decreased by 36%). We change the pharmacokinetics of venlafaxine is not observed. The clinical significance of this fact is unknown.

ketoconazole

pharmacokinetic study in combination with ketoconazole showed an increase of plasma concentrations of venlafaxine and EFA in subjects whose initial metabolism involving CYP2D6 isoenzyme is both good (X-Met), and poor (P-Met). In particular, Cmax venlafaxine increased by 26% in the X-Met and 48% for P-Met. EFA Cmax values increased 14% and 29% in subjects X-Met-Met and P, respectively. Venlafaxine AUC increased by 21% in the X-Met and 70% for P-Met. EFA AUC values increased 23% and 33% in subjects X-Met-Met and P, respectively.

Medications for blood clotting and platelet function (NSAIDs, aspirin and other drugs anticoagulants)

Serotonin, catching platelets plays an important role in hemostasis (stopping bleeding). Epidemiological studies show a relationship between the intake of psychotropic drugs that interfere with serotonin reuptake and the frequency of bleeding in the upper gastrointestinal tract. This relationship is enhanced when both are used nonsteroidal anti-inflammatory drugs (NSAIDs), medicines containing aspirin or other anticoagulants. Proven to increase the risk of bleeding when SSRIs and SNRIs appointment (including venlafaxine) concurrently with warfarin. Patients who are prescribed warfarin, should be carefully monitored prothrombin time and / or partial thromboplastin time, especially when starting or ending concomitant use with venlafaxine.

Interaction with other drugs at the level of study of the metabolism with isozymes of the cytochrome P450

The main pathway include venlafaxine isoenzymes CYP2D6 and CYP3A4: the first of them turns to its active venlafaxine metabolite EFA and the second is less important in the metabolism of venlafaxine compared with CYP2D6 and forms a product with N-desmetilvenlafaksin little pharmacological activity. Preclinical studies have shown, and then it has been confirmed clinically that venlafaxine is a relatively weak inhibitor of CYP2D6. Therefore, even when assigning a moderate suppressive activity of this enzyme drugs (see. The above example imipramine), or in the case of patients with genetically determined reduction CYP2D6 function correction dose of venlafaxine is not required, since the total concentration of the active substance and the active metabolite (venlafaxine and EFA) at the same time does not change. It positively characterizes venlafaxine compared with other antidepressants. Care should be taken while appointing such inhibitors CYP2D6, like quinidine, paroxetine, fluoxetine, haloperidol, perphenazine, levomepromazine, since in this case venlafaxine potentially increase the plasma concentration of these substrates CYP2D6. In combination with medicines, depressing both the enzyme (CYP2D6 and CYP3A4), need to be very careful. Such drug interactions are not sufficiently studied, and the combination drug is not recommended in this case.

Moreover, not venlafaxine inhibits the enzyme activity of CYP3A4, CYP1A2 and CYP2C9, therefore such drugs like alprazolam, caffeine, carbamazepine, diazepam, tolbutamide, terfenadine significant interaction was observed.

Interaction with ketoconazole described above. A similar influence can have such inhibitors of CYP3A3 / 4, itraconazole, ritonavir.

Other interactions associated with various therapeutic and dietary factors

Against the background of venlafaxine should be particularly careful when electroconvulsive therapy, as the experience with venlafaxine in these conditions is missing.

Significant influence of different kinds of food on the absorption of venlafaxine and its subsequent transformation into the EFA is not revealed. The food (usually high in protein, such as hard cheeses, fish, eggs, turkey), as well as nutritional supplements and fitness diets, which are high source of tryptophan, potentially contributes bólshey develop in the body of serotonin, which may increase side serotonergic effects of venlafaxine .

Undesirable pharmacodynamic interactions may occur while taking Venlafaxine concurrently with medicinal herb St John's wort (herb or medications of different kinds of it), this combination is not recommended.

There have been reports of false positive results of urine immunochromatographic rapid test (test strips) to phencyclidine and amphetamines in patients receiving venlafaxine, and even a few days after discontinuation of venlafaxine. This can be explained by the lack of specificity of this test. To distinguish from venlafaxine phencyclidine and amphetamines can only confirmatory test in a specialized anti-doping laboratory.

According to the data available to date, venlafaxine did not show itself as a drug that causes drug abuse or addiction (both at the preclinical study affinity receptors, as well as in clinical practice).

special instructions for Venlafaxine

Suicide and suicidal behavior

Depression is associated with an increased risk of suicidal thoughts, self-inflicted injuries and suicide (suicidal behavior). This risk persists until the onset of severe remission. As in the first few weeks of therapy, or even longer periods of time, improvement can not be observed, prior to such improvements need to closely monitor the patients. According to the accumulated clinical experience of suicide risk may increase in the early stages of recovery.

Patients with a history of suicide attempts, or with high levels of suicidal thoughts on topics before treatment to greater risk of suicidal thoughts or suicide attempts, such patients should be carefully monitored. A meta-analysis of placebo-controlled clinical trials of antidepressants involving adult patients with psychiatric disorders showed that when taking antidepressants compared to placebo in patients younger than 25 years are at increased risk of suicidal behavior. Drug treatment of patients and in particular patients with high suicide risk, must be accompanied by careful observation, especially early in therapy and dose adjustment. Patients (and caregivers of such patients) should be warned about the need to monitor any manifestations of clinical worsening, suicidal behavior or thoughts and unusual changes in behavior and to seek immediate medical attention if these symptoms.

A small number of patients taking antidepressants, including venlafaxine, aggression may occur during treatment initiation, dose change or discontinuation of treatment.

Conducted to date clinical studies revealed no tolerance to venlafaxine or depending on him. Despite this, as in the treatment of other drugs acting on the central nervous system, the physician must establish careful monitoring of patients for signs of drug abuse, as well as patients having a history of symptoms.

Special patient groups

Venlafaxine is not approved for use in children.

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 may occur hypomanic and manic states. As with other antidepressants, venlafaxine should be administered with caution to patients with mania in history. Such patients need medical supervision.

When therapy with venlafaxine may have seizure disorders. As with all antidepressants, venlafaxine should be used with caution in patients with convulsive disorders in history, these patients need to closely monitor. Treatment should be discontinued if seizures develop.

akathisia

The use of venlafaxine has been associated with the development of akathisia, which is characterized by an unpleasant feeling to the patient's internal motor restlessness, and manifests itself in the patient's inability to sit still for a long time in one position for a long time, or remain motionless. This condition can occur at the start of treatment and during the first weeks of treatment. In patients who were such symptoms, increasing the dose is not recommended.

Bipolar disorder

Prior to treatment, it is necessary to identify those patients who are at risk for bipolar disorder. Such screening should include a detailed study of the history, including a family, to detect cases of suicide, bipolar disorder. Note that venlafaxine is not recommended for use in treating bipolar depression.

Use in patients with concomitant diseases

Clinical experience with venlafaxine in patients with concomitant illness is limited.

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

Patients should be warned of the immediate treatment to the doctor with the appearance of the rash, urticaria or other elements of allergic reactions.

In some patients, while taking venlafaxine observed a dose-dependent increase in blood pressure and / or an increase in heart rate, so we recommend regular monitoring of blood pressure and ECG, especially in the period specification or increase the dosage of venlafaxine. In post-marketing experience of the use of venlafaxine (an overdose), fatal cardiac arrhythmias have been reported. Before prescribing venlafaxine to patients at high risk of serious cardiac arrhythmias should weigh the probable benefits to the possible risk in the application.

Patients, especially the elderly, should be alerted to the possibility of dizziness and impaired sense of balance for the purpose of injury prevention.

During reception of venlafaxine, especially in conditions of dehydration or reduction of circulating blood volume (including elderly patients, and patients taking diuretics) can be observed hyponatremia and / or syndrome of inadequate secretion of antidiuretic hormone.

Venlafaxine has not been studied in patients who have had recent heart attacks and suffering from decompensated heart failure. Such patients the drug should be used with caution.

SSRIs or venlafaxine patients with diabetes can cause changes in the level of glucose in the blood plasma. May require correction dose of insulin and / or anti-diabetic drugs.

During treatment advised to refrain from taking any alcoholic beverages.

Safety and efficacy of venlafaxine in combination with drugs that reduce the body weight (including phentermine) have not been established. Not recommended simultaneous venlafaxine and drugs that reduce body weight.

Women of childbearing potential must use appropriate contraceptive methods while taking venlafaxine.

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

Dry mouth is seen in 10% of patients treated with venlafaxine. This may increase the risk of tooth decay. Patients should carefully observe good oral hygiene.

The use of venlafaxine can cause akathisia development, characterized by subjective discomfort or restlessness and need to move often, it is often accompanied by an inability to sit or stand still. This mainly occurs in the first few weeks of treatment. Increasing doses in patients who develop these symptoms can cause unwanted effects.

In placebo-controlled clinical trials in 5.3% of patients with clinically significant increase in the cholesterol content in the serum were recorded. Necessary to control cholesterol levels during long-term treatment.

withdrawal

During the cessation of treatment is common withdrawal symptoms, especially if abrupt end. The risk of withdrawal may depend on several factors, including the duration of treatment, and the magnitude of the therapeutic dose rate of reduction. Very rarely reported these symptoms in patients who have inadvertently missed taking the drug.

Symptoms of the syndrome usually occurs within the first few days after stopping treatment. Usually these symptoms disappear within 2 weeks, although some people may be 2-3 months or more. It is recommended to gradually reduce the dose of venlafaxine for discontinuation of the drug - for a few weeks or months, depending on the severity of clinical symptoms.

serotonin syndrome

Admission venlafaxine, as well as other serotonergic drugs may cause serotonin syndrome, a potentially life-threatening condition, especially with simultaneous use of other drugs that may affect the serotonergic neurotransmitter systems, such as MAO inhibitors (see. "The interaction profile with other drugs ").

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

Effects on driving ability and work with the mechanisms

During treatment, care must be taken when performing potentially dangerous types of work that require high concentration and speed of psychomotor reactions (including driving and operating machinery).

Release form of Venlafaxine

Tablets of 37.5 mg or 75 mg.

10 tablets in blisters of PVC film and aluminum foil printed patent.

1, 2, 3, 4 or 5, the contour of cellular packaging together with instructions for use are placed in a pile of cardboard.

Storage conditions ofVenlafaxine

In a dry, dark place at a temperature no higher than 25 ° C.

Keep out of the reach of children.

Shelf life of Venlafaxine

3 years.

Do not use beyond the expiration date printed on the package.

Conditions of supply of Venlafaxine from pharmacies

With prescription.