Expiration date: 06/2025

The composition and form of issue:

Tablets. 1 tablet contains active substance:

venlafaxine hydrochloride 42.43 mg (corresponding to 37.5 mg venlafaxine)

84.86 mg (corresponds to 75 mg venlafaxine)

excipients: MKC — 64, 72/129, 44 mg of corn starch — 30/60 mg iron oxide yellow (E172) — 0, 1/0, 2 mg sodium carboximetilkrahmal — 22, 5/45 mg of talc — 1, 5/3 mg silica colloidal anhydrous — 2, 25/4, 5 mg of magnesium stearate — 1, 5/3 mg

in blisters of PVC film and aluminum foil, 14 PCs. in cardboard pack 2, or 4 blisters.

Description pharmaceutical form:

Pills 37.5 mg: oblong pill light yellow with valium on both sides.

Tablets 75 mg: round tablets of light yellow color, with valium on one side and engraving "PLIVA" on the other.

Feature:

On chemical structure is a racemate of two active enantiomers (does not belong to one class of antidepressants — tricyclic, tetracyclic, etc.).

Pharmacokinetics:

Well absorbed from the gastrointestinal tract. After receiving a single dose of 25-150 mg Cmax in the blood plasma is 33-172 ng/ml, respectively, and is achieved within about 2, 4 h.

Subjected to intensive metabolism at the first passage through the liver. Its main metabolite — O-desmethylvenlafaxine (EFA).

Cmax of ODV in plasma is 61-325 ng/ml, respectively, and was reached by approximately 4, 3 h after administration.

Binding venlafaxine and EFA with blood plasma proteins is 27 and 30%, respectively.

When repeated administration of the equilibrium concentrations venlafaxine and ODV are attained within 3 days. After taking the drug at mealtime the time to reach Cmax in plasma is increased by 20-30 min, but the magnitude of the Cmax and absorption do not change.

EFA and other metabolites, as well as nematerializiranih venlafaxine excreted by the kidneys. T 1/2 venlafaxine and ODV are 5 and 11 h, respectively.

In patients with cirrhosis concentration venlafaxine and ODV in plasma are elevated and the rate of excretion is reduced. In moderate and severe renal failure, total clearance venlafaxine and EFA decreases and the half-life is lengthened. The decrease of the main clearance is observed, mostly 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 action of the drug associated with its ability to potentiate the transmission of nerve impulses in the Central nervous system. Venlafaxine and ODV are potent inhibitors of reverse takeover serotonin and noradrenalina (ISSN) 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.

Has no affinity for muskarinovymi, cholinergic, histamine (H1) and alpha1-adrenergic receptors in the brain. Does not inhibit MAO activity. Has no affinity to opioid, benzodiazepinovym or N-methyl-d-aspartate (NMDA) receptors.

Indications:

Depression of various etiologies (treatment and prevention).

Contraindications:

• hypersensitivity
  
• simultaneous reception of MAO inhibitors (see "Interactions")
  
• a severe violation of the kidney and/or liver (glomerular filtration rate, GFR less than 10 ml/min)
  
• the age of 18 years (safety and efficacy for patients in this age group is not proven)
  
• established or suspected pregnancy
  
• lactation.
  

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 has not been proven, therefore its application 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, they should immediately consult a doctor in the event of or planning pregnancy during the period of drug treatment.

Venlafaxine and ODV are 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, newborns may experience withdrawal symptoms of the drug.

Side effects:

Most of these side effects depends on the dose. During prolonged treatment severity and frequency of most of these effects are reduced, and does not need discontinuation of therapy.

In order to reduce the frequency of side effects is distributed: 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, seldom — hepatitis.

From the metabolic: increased cholesterol levels in serum, decrease of body weight, sometimes changing the results of laboratory tests of liver function, hyponatremia, syndrome of inadequate secretion of antidiuretic hormone.

From the side of cardiovascular system: hypertension, flushing of the skin, postural hypotension, tachycardia.

CNS: unusual dreams, dizziness, insomnia, anxiety, paresthesia, stupor, increased muscle tone, tremor, yawning sometimes — apathy, hallucinations, muscle spasms, serotonin syndrome, rarely 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, impaired vision, rarely — violation of taste sensations.

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

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

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

After the abrupt cancellation venlafaxine or reduced doses may occur: 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, but because of the likelihood of the reduction in dose should be gradual.

Drug interactions:

Simultaneous use of MAO inhibitors is contraindicated and venlafaxine. Receiving Felafacs 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 7 days after drug withdrawal Velofax.

Venlafaxine does not affect the pharmacokinetics of lithium.

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

When used together with haloperidol enhanced the effect of the latter due to the increase in the level of drug in the blood.

While the use of diazepam pharmacokinetics drugs and their main metabolites does not change significantly. Also there was no effect on 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 there is no experience of application venlafaxina in these conditions.

Drugs, metaboliziruemah isoenzymes of cytochrome P 450: the CYP2D6 enzyme of the cytochrome P 450 converts the venlafaxine to the active metabolite, ODV. 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 the appointment of patients with genetically determined reduced activity of CYP2D6, since the total concentration venlafaxine and EFA will remain the same.

The main route of excretion venlafaxine includes metabolism involving CYP2D6 and CYP3A4, so caution should be exercised when assigning venlafaxine PM, depressing both these of enzyme. Such drug interactions have not been investigated.

Venlafaxine is a relatively weak inhibitor CYP1D6 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 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 (including beta - blockers, ACE inhibitors and diuretics) and anti-diabetic drugs are not detected.

Linking blood plasma proteins is to venlafaxine — 27% for the EFA — 30%. Therefore, the drug does not affect the concentration of drugs having a high degree of protein binding in plasma.

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. The clinical significance of this effect is unknown.

Method of application and dose:

Inside, during a meal, preferably at the same time, not chewing and drinking fluid.

For the treatment of depression the recommended initial dose of Felafacs — 37, 5 mg 2 times a day, every day. If after a few weeks of treatment, there is no significant improvement, the dose can be increased to 150 mg/day 75 mg 2 times a day.

If necessary, the drug at a higher dose in severe depressive disorder or other conditions requiring inpatient treatment, you can immediately assign 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. The maximum daily dose of Felafacs is 375 mg. After achieving the desired therapeutic effect daily dose can be gradually reduced to the minimum effective level.

Maintenance treatment continues for 6 months or more. The drug is prescribed in the lowest effective dose used in the treatment of a depressive episode.

In renal insufficiency, mild (glomerular filtration rate over 30 ml/min) correction mode is not required.

When kidney failure of moderate severity (glomerular filtration rate of 10-30 ml/min) dose should be reduced by 25-50%. In connection with the lengthening of T1/2 venlafaxine and its active metabolite such patients should take the entire dose 1 time per day.

In renal failure, severe (glomerular filtration rate less than 10 ml/min) the use of Felafacs not recommended, because the experience of such therapy is limited.

Patients undergoing hemodialysis, can receive 50% the usual daily dose venlafaxine after the completion of hemodialysis.

In mild hepatic insufficiency (PV less than 14 C) correction mode is not required.

When moderate hepatic insufficiency (PV 14 to 18) the dose should be reduced by 50%.

In severe hepatic insufficiency, the use of Felafacs not recommended, because the experience of such therapy is limited.

Elderly patients dose adjustment is not required, but (as with the appointment of other drugs) in the treatment requires caution, for example in connection with the possibility of renal dysfunction. Therefore, elderly patients should use the lowest effective dose, if necessary increasing the dose shows careful medical supervision.

Cessation of the drug Velofax: at the end of the treatment dose is reduced gradually. When used in a dose equal to or greater than 75 mg, the rate of more than 7 days, cancel the drug for at least a week, gradually reducing the dose. When used in high doses over the course of 6 weeks, the period required for full discontinuation of the drug, is at least 2 weeks. Symptoms of recurrence of the disease within the cancellation period of Felafacs requires the appointment of the initial dose or a more gradual and prolonged decline.

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 Velofax: 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 the dose. The length of time required to reduce the dose depends on its magnitude, duration, and individual sensitivity of the patient.

When assigning tablets Velofax patients with lactose intolerance consider lactose content (84, 93 mg each tablet contains 37 5 mg 169, 86 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) 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 clarify or increase dose.

An increase in heart rate, primarily while receiving high doses. Recommended caution in tachyarrhythmias.

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

Like other SSRI's, 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.

To date clinical trials have not revealed tolerance to venlafaxine or dependent on him. Despite this, as with the treatment of other drugs acting on the Central nervous system, a doctor must conduct a careful monitoring of patients for signs of abuse of the drug. Careful monitoring is necessary 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 judgement, 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.