Expiration date: 03/2025

The composition and form of issue:

Tablets. 1 tablet contains:

venlafaxine (as hydrochloride) 37.5 mg or 75 mg

excipients: calcium hydrogen phosphate anhydrous, lactose anhydrous, sodium starch of glycolate magnesium stearate silicon dioxide colloidal anhydrous dye Red Iron Oxide (E172)

blistere in 10 PCs. in cardboard pack 3 blisters.

Description pharmaceutical form:

Pills 37.5 mg: light-pink valium pill with dark pink splashes, chamfered and scored on one side.

Tablets 75 mg: light pink valium pill with pink speckles, bevelled and scored on one side.

Feature:

Antidepressant, which is a racemate of two active enantiomers.

Pharmacokinetics:

Venlafaxine is well absorbed from the gastrointestinal tract. After a single dose of 25-150 mg Cmax in the blood plasma reaches 33-172 ng/ml within about 2, 4 h is Subjected to intensive metabolism when "first pass" through the liver. Its main metabolite — O-desmethylvenlafaxine (EFA). T1/2 venlafaxine and ODV are 5 and 11 h, respectively. Cmax of ODV in plasma 61-325 ng/ml was reached by approximately 4, 3 h after injection venlafaxine. Binding venlafaxine and EFA with blood plasma proteins — 27 and 30%, respectively. EFA and other metabolites, as well as nematerializiranih venlafaxine are excreted by the kidneys. When repeated administration of the equilibrium concentrations venlafaxine and ODV are attained within 3 days. In the range of daily doses 75-450 mg, venlafaxine and EFA are linear kinetics. After taking the drug during meals, the time to maximum concentration in plasma is increased by 20-30 minutes, but the magnitude of maximum concentration and absorption is not changed.

In patients with cirrhosis concentration in blood plasma venlafaxine and EFA enhanced, and the rate of excretion is reduced. In moderate or severe renal failure, total clearance venlafaxine and EFA decreases and the half-life is lengthened. The decrease in total clearance is mainly observed in patients with Cl creatinine <30 ml/min.

The age and sex of the patient does not affect the pharmacokinetics of the drug.

Description pharmacological action:

The mechanism of antidepressant effects of the drug associated with its ability to potentiate the transmission of nerve impulses in the Central nervous system. Venlafaxine and its major metabolite ODV are potent inhibitors of reverse takeover serotonin and norepinephrine (SNRI) and weak inhibitors of dopamine reuptake. In addition, venlafaxine and ODV reduce beta-adrenergic reactivity after a single injection and continuous technique. Venlafaxine and ODV are equally effectively affect the reuptake of neurotransmitters.

Venlafaxine has no affinity for muskarinovymi, cholinergic, histamine-H1 and &alpha-adrenergic receptors in the brain. Venlafaxine does not inhibit MAO activity. Has no affinity to opioid, benzodiazepinovym, phencyclidine or N-methyl-d-aspartate (NMDA) receptors.

Indications:

Depression of various etiologies (treatment and prevention).

Contraindications:

• hypersensitivity
  
• simultaneous reception of MAO inhibitors (see also section "Interactions")
  
• severe violations of the kidneys and/or liver (glomerular filtration rate (GFR) <10 ml/min)
  
• the age of 18 years (safety and efficacy for this age group is not proven)
  
• established or suspected pregnancy
  
• the period of breastfeeding.
  

With caution:

• recent myocardial infarction
  
• unstable angina
  
• hypertension
  
• tachycardia
  
• convulsive syndrome in history
  
• increased intraocular pressure
  
• angle-closure glaucoma
  
• manic States in history
  
• the predisposition to bleeding from skin and mucous membranes
  
• initially reduced body weight.
  

Application of pregnancy and breast-feeding:

The safety of venlafaxine during pregnancy is not proven, therefore the use during pregnancy (or suspected pregnancy) is possible only if the potential benefit to the mother outweighs the potential risk to the fetus. Women of childbearing age should be warned about this before starting treatment and should immediately consult doctor in case of pregnancy or planning a pregnancy during the period of drug treatment.

Venlafaxine and its metabolite ODV is allocated in breast milk. The safety of these substances for infants not proven, therefore venlafaxine during breastfeeding is not recommended. If necessary, the drug during lactation should decide the issue of termination of breastfeeding. If the treatment of the mother was completed shortly before birth, the newborn may experience withdrawal symptoms of the drug.

Side effects:

Most of the following side effects are dose-dependent. During prolonged treatment severity and frequency of most of these effects is reduced, and does not need discontinuation of therapy.

In order of decreasing frequency: often (&ge1%), sometimes (&ge0, 1–<1%), rare (&ge0, 01–<0, 1%), very rarely (<0, 01%).

Common symptoms: weakness, fatigue.

Gastrointestinal: loss of appetite, constipation, nausea, vomiting, dry mouth rare — hepatitis.

From the metabolic: the increase in level of cholesterol of blood serum, decrease of body weight and sometimes change in laboratory tests of liver function, hyponatremia, syndrome of inadequate secretion of antidiuretic hormone.

From the side of cardiovascular system: arterial hypertension, sometimes — postural hypotension, tachycardia.

From the nervous system: unusual dreams, dizziness, insomnia, anxiety, paresthesia, stupor, increased muscle tone, tremor, yawning sometimes — apathy, hallucinations, muscle spasms, serotonin syndrome is rare — epileptic seizures, manic reaction, and symptoms resembling neuroleptic malignant syndrome.

From the urogenital system: violation of ejaculation, erection, anorgasmia, dysuric disorders (mostly — difficulty in beginning urination) and sometimes — decreased libido, menorrhagia, urinary retention.

From the sensory organs: violation ccomodation, mydriasis, blurred vision sometimes — a violation of taste sensations.

With the skin: flushing of the skin sweating and sometimes photosensitivity reaction, rarely — erythema multiforme, Stevens-Johnson syndrome.

From the blood system and the blood: sometimes — bleeding into the skin (ekhimozy) and mucous membranes, thrombocytopenia, rarely prolongation of bleeding time.

Hypersensitivity reactions: sometimes — skin rash very rare — anaphylactic reactions.

After the abrupt cancellation venlafaxine or decrease in dose can occur: fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, irritability, disorientation, hypomania, paresthesia, sweating. These symptoms are usually mild and go away without treatment. Because of the likelihood of occurrence of these symptoms it is very important to gradually reduce the dose.

Drug interactions:

Simultaneous use of MAO inhibitors is contraindicated and venlafaxine. The drug Venlaxor can begin not less than 14 days after the end of therapy MAO inhibitors. If you used a reversible MAO inhibitor (moclobemide), this interval may be shorter (24 h). Therapy MAO inhibitors can begin not less than 7 days after discontinuation of the drug Venlaxor.

Venlafaxine does not affect the pharmacokinetics of lithium.

While the use of imipramine pharmacokinetics venlafaxine and its metabolite EFA does not change.

Haloperidol: the effect may arise due to the increase in the level of drug in the blood when used together.

While the use of diazepam pharmacokinetics drugs and their main metabolites does not change significantly. Also there was no effect in psychomotor and psychometric effects of diazepam.

While the use of clozapine may experience elevated levels in blood plasma and the development of side effects (e.g. seizures).

With simultaneous use of risperidone (despite the increase in AUC of risperidone) pharmacokinetics of the amount of the active components (risperidone and its active metabolite) did not change significantly.

Enhances the effect of alcohol on psychomotor reactions.

On the background of venlafaxine should be cautious when electroconvulsive therapy, because. experience with the use venlafaxina in these conditions is lacking.

Drugs, metaboliziruemah by cytochrome P450 isoenzymes: in contrast to many other antidepressants, the dose venlafaxina can not be reduced by simultaneous administration with drugs that inhibit the activity of CYP2D6, or in patients with a genetically determined reduced activity of CYP2D6 (CYP2D6 enzyme of the cytochrome P450 converts the venlafaxine to the active metabolite EFA), since the total concentration of active substances and metabolite (venlafaxine and EFA) do not change.

The main route of excretion venlafaxine includes metabolism involving CYP2D6 and CYP3A4 and should be used with particular caution in the appointment venlafaxine in combination with drugs, oppressive both these of enzyme. Such drug interactions have not been investigated.

Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not inhibit the activity of isoenzymes CYP1A2, CYP2C9 and CYP3A4, therefore, should not expect its interaction with other drugs, in the metabolism involving these hepatic enzymes.

Cimetidine inhibits the metabolism "first pass" venlafaxine and has no effect on the pharmacokinetics of ODV. In the majority of patients is expected only a slight increase in the total pharmacological activity venlafaxine and EFA (more pronounced in older patients and in the liver).

Clinically significant interactions with antihypertensive venlafaxine (including beta-blockers, ACE inhibitors and diuretics) and anti-diabetic drugs are not detected.

Drugs associated with blood plasma proteins: plasma protein binding is 27% for venlafaxine and 30% for EFA, therefore, impact on the concentration in plasma drugs with a high degree of protein binding have not been identified.

While concurrent use with warfarin may increase the anticoagulant effect of the latter.

While admission varies with indinavir the pharmacokinetics of indinavir (28% decrease in AUC and 36% decrease in Cmax), and the pharmacokinetics venlafaxine and EFA does not change. However, the clinical significance of this effect is unknown.

Method of application and dose:

Inside, during a meal.

The recommended initial dose of 75 mg in 2 doses (37, 5 mg) daily. If after a few weeks of treatment, there is no significant improvement, the daily dose can be increased to 150 mg (on 75 mg 2 times a day). If, in the opinion of the doctor, a higher dose (severe depressive disorder or other condition, requiring inpatient treatment), you can assign 150 mg in 2 doses (75 mg 2 times a day). Then the daily dose can be increased by 75 mg every 2-3 days until the desired therapeutic effect. Maximum daily dose of 375 mg. After achieve the desired therapeutic effect may gradually decrease the daily dose to the minimum effective level.

Supportive therapy and relapse prevention: maintenance treatment may continue for 6 months or more. Are assigned the minimum effective dose used in the treatment of a depressive episode.

Renal insufficiency: in mild renal failure (GFR is >30 ml/min) correction mode is not required. When moderate renal insufficiency (GFR is 10-30 ml/min) dose should be reduced by 25-50%. In connection with the prolongation of half-life venlafaxine and its active metabolite ODV, such patients should take the entire dose 1 time per day. Not recommended for use venlafaxine in severe renal failure (GFR of <10 ml/min), since reliable data on such therapy do not exist. Patients on hemodialysis can receive 50% the usual daily dose venlafaxine after the completion of hemodialysis.

Hepatic failure: in mild hepatic insufficiency (PV — <14 C) correction mode is not required. When moderate hepatic insufficiency (PV — 14 to 18) the dose should be reduced by 50%. Not recommended for use venlafaxine in severe hepatic insufficiency, since reliable data on such therapy do not exist.

Elderly patients: the mere old age of the patient does not require modification of the dose but (as in the appointment of other drugs) in the treatment of elderly patients requires caution, for example in connection with the possibility of renal dysfunction. You should apply the lowest effective dose. If the dose the patient should be under close medical supervision.

Cessation of the drug Venlaxor:

At the end of the drug Venlaxor recommended to gradually reduce the dosage, at least during the week, and observe the patient's condition in order to minimize the risk associated with the withdrawal of the drug (see below).

The period required for full discontinuation of the drug depends on its dose, duration of treatment and the individual patient.

Overdose:

Symptoms: ECG changes (elongation QT interval, blockade feet beam Guisa, the expansion of the complex QRS), sinus or ventricular tachycardia, aetiology, hypotension, apnoea condition, the change of consciousness (decreased alertness). In case of overdose venlafaxine at simultaneous reception with alcohol and/or other psychotropic drugs reported fatality.

Treatment: symptomatic. Specific antidotes are unknown. It is recommended that continuous monitoring of vital functions (respiration and circulation). The appointment of activated charcoal to reduce absorption of the drug. It is not recommended to induce vomiting in connection with the danger of aspiration. Venlafaxine and EFA are not displayed by dialysis.

Special instructions:

Withdrawal of the drug Venlaxor: as with treatment with other antidepressants, abrupt cessation of therapy with venlafaxine, especially after high doses of the drug can cause symptoms cancellation, and therefore recommended before removal of the drug gradually reduce its dose. The length of time required to reduce the dose depends on the dose, duration of therapy, and also individual sensitivity of the patient.

When assigning tablets Venlaxor patients with lactose intolerance should take into account the content of lactose in the formulation (30 mg in each tablet 37, 5 mg 60 mg each tablet 75 mg).

Patients with depressive disorders before starting any drug therapy should take into account the likelihood of suicide attempts. Therefore, to reduce the risk of overdose the initial dose should be as low as possible, and the patient should be under close medical supervision.

In patients with affective disorders during treatment with antidepressants, including venlafaxine, you may experience hypomanic or manic state. As with other antidepressants, venlafaxine should be administered with caution to patients with delusions in history. Such patients require medical monitoring.

As with other antidepressants, venlafaxine should be administered with caution to patients with epileptic in history. Treatment with venlafaxine should be discontinued at the occurrence of epileptic seizures.

Patients should be warned about the necessity to immediately consult a doctor if you experience rash, urticaria or other allergic reactions.

Some patients during venlafaxine marked dose-dependent increase in blood pressure, therefore it is recommended that regular monitoring AD, especially during the selection of or increase in dosage.

An increase in heart rate, especially while taking high doses. Recommended caution in tachyarrhythmias.

Patients, especially the elderly, should be warned of the possibility of dizziness and disorders of balance.

Like other inhibitors of serotonin reuptake, venlafaxine may increase the risk of bleeding in the skin and mucous membranes. When treating patients predisposed to such conditions, caution is necessary.

During with venlafaxine, especially in dehydration or reduction in blood volume (including in elderly patients and patients taking diuretics), you may experience hyponatremia and/or syndrome of inadequate secretion of antidiuretic hormone.

While taking the drug may experience mydriasis, therefore it is recommended that control of intraocular pressure in patients who tend to its increase or suffering from angle-closure glaucoma.

Venlafaxine has not been investigated in patients who have had a recent myocardial infarction and suffering from decompensated heart failure. In such patients the drug should be administered with caution.

You must install the monitoring of patients for signs of abuse of the drug, especially for patients with a history of such symptoms.

Women of childbearing age must use appropriate contraceptive methods during the venlafaxine.

Despite the fact that venlafaxine does not affect psychomotor and cognitive function, be aware that any drug therapy psychoactive drugs may reduce the ability of making judgments, thinking or performing motor functions. This should be mentioned to the patient before starting treatment. If you experience such effects, the extent and duration of the restrictions must be established by a physician. Also not recommended to drink alcohol.