Velafax, pills 75mg 28pcs

Composition

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Auxiliary substances:

microcrystalline cellulose,

corn starch,

yellow iron oxide dye (E 172),

sodium carboxymethyl starch,

talc,

colloidal silicon dioxide,

magnesium stearate.

Pharmacological action

An antidepressant that is not chemically related to any class of antidepressants (tricyclic, tetracyclic or other) is a racemate of two active enantomers. The mechanism of antidepressant action of the drug is associated with its ability to potentiate the transmission of a nerve impulse to the central nervous system.

Venlafaxine and its major metabolite O-desmethylvenlafaxine (EFA) are strong serotonin and norepinephrine reuptake inhibitors and weak dopamine reuptake inhibitors. In addition, venlafaxine and EFA reduce beta-adrenergic reactivity both after a single use and with continuous use. Venlafaxine has no affinity for m-cholinergic, histamine H1-receptors and α1-adrenergic receptors of the brain. It does not suppress MAO activity. The drug does not affect the release of norepinephrine from brain tissue.

Suction

After oral use, venlafaxine is well absorbed from the gastrointestinal tract. After a single dose of 25-150 mg, Cmax is reached within approximately 2.4 hours and is 33-172 ng / ml. After taking the drug with a meal, the time to reach Cmax in blood plasma increases by 20-30 minutes, but the values of Cmax and absorption do not change.

Distribution

The binding of venlafaxine and EFA to plasma proteins is 27% and 30%, respectively. With repeated use of Css venlafaxine and EFA are achieved within 3 days.

Metabolism

It undergoes intensive metabolism during the” first pass ” through the liver. The main metabolite is O-desmethylvenlafaxine. Cmax EFA in blood plasma is reached approximately 4.3 hours after use and is 61-325 ng / ml.

In the daily dose range of 75-450 mg, the pharmacokinetics of venlafaxine and EFA are linear.

Elimination

of T 1/2 venlafaxine and EFA is 5 and 11 hours, respectively. EFA and other metabolites, as well as unchanged venlafaxine, are eliminated by the kidneys. With repeated use of Css venlafaxine, EFA is achieved within 3 days.

Pharmacokinetics in special clinical cases

In patients with cirrhosis of the liver, plasma concentrations of venlafaxine and EFA are increased, and the rate of their elimination is reduced.

In moderate or severe renal insufficiency (creatinine clearance less than 30 ml / min), the total clearance of venlafaxine and EFA decreases, and T 1/2 increases.

The patient’s age and gender do not affect the pharmacokinetics of the drug.

Indications

-treatment of depressions of various etiologies, including depression accompanied by symptoms of anxiety.

Use during pregnancy and lactation

During pregnancy (including before childbirth), venlafaxine is contraindicated, since the safety of its use during this period has not been determined.

Venlafaxine and the EFA metabolite are excreted in breast milk. The safety of these substances for newborns has not been proven, so if you need to take the drug during lactation, you should stop breastfeeding for the duration of treatment.

Contraindications

-severe renal dysfunction (creatinine clearance less than 10 ml / min) and / or liver;

– children and adolescents under 18 years of age;

— pregnancy;

– lactation (breastfeeding);

– simultaneous use of MAO inhibitors;

– individual intolerance to venlafaxine and other components of the drug.

Use with caution in the case of a recent myocardial infarction, unstable angina, arterial hypertension, tachycardia, convulsive syndrome in the anamnesis, increased intraocular pressure, angle-closure glaucoma, manic state in the anamnesis, hyponatremia, hypovolemia, dehydration, concomitant use of diuretics, suicidal tendencies, predisposition to bleeding (from the skin and mucous membranes), at baseline reduced body weight.

Side effects

Most of the side effects listed below are dose-dependent. With long-term treatment, the severity and frequency of most of these effects are reduced, and there is no need to cancel therapy.

Frequency of side effects: very common (≥10%), common (≥1%, but

From the digestive system:  often-decreased appetite, constipation, nausea, vomiting, dry mouth, dyspepsia, abdominal pain; infrequently-bruxism, increased activity of hepatic transaminases; rarely-hepatitis; in some cases – pancreatitis.

From the side of metabolism:  often-an increase in the level of serum cholesterol (especially after prolonged use or taking the drug in high doses), a decrease or increase in body weight; infrequently – hyponatremia, a syndrome of insufficient secretion of antidiuretic hormone (ADH); in some cases – an increase in the level of plasma prolactin.

From the cardiovascular system:  often-increased blood pressure, hyperemia of the skin; infrequently-decreased blood pressure, postural hypotension, syncope, arrhythmia, tachycardia; very rarely – arrhythmia of the “pirouette” type, prolongation of the QT interval, ventricular tachycardia, ventricular fibrillation.

From the central nervous system and peripheral nervous system:  often – dizziness, asthenia, nightmares, weakness, dizziness, insomnia, drowsiness, increased nervous excitability, paresthesia, stupor, muscle hypertonicity, tremor, yawning, sedation; infrequently – apathy, hallucinations, myoclonus, fainting; rarely – convulsions, ataxia with impaired balance and coordination of movement, speech disorders, mania or hypomania, serotonin syndrome, symptoms that resemble neuroleptic malignant syndrome, epileptic seizures; in some cases – delirium, extrapyramidal disorders, including dyskinesia and dystonia, tardive dyskinesia, psychomotor anxiety/akathisia.

From the side of mental status:  the frequency has not been established – depression, suicidal thoughts and suicidal behavior during therapy and after discontinuation of the drug.

Hematopoietic and lymphatic system disorders:  infrequently – hemorrhages in the skin (ecchymosis) and mucous membranes, thrombocytopenia, prolongation of bleeding time, hemorrhagic syndrome; in some cases-agranulocytosis, aplastic anemia, neutropenia and pancytopenia.

From the urinary system:  often-violation of urination; infrequently-urinary retention.

From the side of the reproductive system:  often-decreased libido, erectile and/or ejaculatory disorders, anorgasmia in men, menorrhagia; infrequently – menstrual disorders, anorgasmia in women.

From the side of the senses:  often – accommodation disorders, mydriasis, visual disturbances, noise or ringing in the ears; infrequently-taste disorders.

From the side of the skin and its appendages:  often – excessive sweating (including night sweats); infrequently-alopecia.

Respiratory system disorders:  infrequently-shortness of breath; in some cases – pulmonary eosinophilia.

From the endocrine system:  rarely-galactorrhea; in some cases – increased prolactin levels.

Allergic reactions:  infrequently-skin rash (including maculopapular), pruritus, photosensitization, angioedema, urticaria; rarely-erythema multiforme, Stevens-Johnson syndrome; in some cases-anaphylactic reactions.

Musculoskeletal disorders:  often-arthralgia, myalgia; infrequently-muscle spasms; in some cases-rhabdomyolysis.

After abrupt withdrawal of venlafaxine or reduction of the dose, increased fatigue, drowsiness, asthenia, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, unusual dreams, difficulty falling asleep, restlessness, anxiety, irritability and emotional lability, paresthesia, confusion, disorientation, hypomania, tremor, paresthesia, increased sweating, tachycardia, convulsions, ringing or tinnitus, refusal to eat. To prevent the development of withdrawal symptoms, it is very important to gradually reduce the dose of the drug, especially after taking high doses.

Interaction

Concomitant use of MAO inhibitors and venlafaxine is contraindicated. Venlafaxine should be started no earlier than 14 days after the end of MAO inhibitor therapy. If a reversible MAO inhibitor (moclobemide) was used, this interval may be shorter (24 hours). Therapy with MAO inhibitors can be started no earlier than 7 days after venlafaxine is discontinued.

Concomitant use of venlafaxine with lithium preparations may increase the level of lithium in the blood.

When co-administered with imipramine, the pharmacokinetics of venlafaxine and its EFA metabolite do not change. Venlafaxine does not affect the metabolism of imipramine and its metabolite 2-hydroxyimipramine, but increases the plasma AUC and Cmax of desipramine (the main metabolite of imipramine), and also reduces the renal clearance of 2-hydroxydesipramine. The clinical significance of this phenomenon is unknown.

When used concomitantly with neuroleptics, symptoms resembling neuroleptic malignant syndrome may occur.

Venlafaxine reduces the renal clearance of haloperidol by 42%, while AUC and Cmax values increase by 70% and 88%, respectively. The effects of haloperidol may be enhanced.

The pharmacokinetics of drugs and their main metabolites do not change significantly when used concomitantly with diazepam.

When used concomitantly with clozapine, an increase in its plasma level and the development of side effects (for example, epileptic seizures) may occur.

When used concomitantly with risperidone, despite an increase in the AUC of the drug, the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) did not change significantly.

Concomitant use of ethanol and venlafaxine was not associated with a decrease in mental and motor activity. Despite this (as in the case of taking other drugs that affect the central nervous system), the use of ethanol is not recommended during venlafaxine therapy.

Cimetidine suppresses the metabolism of venlafaxine during the” first pass ” through the liver and does not affect the pharmacokinetics of EFA. In most patients, only a slight increase in the overall pharmacological activity of venlafaxine and EFA is expected (more pronounced in elderly patients and in patients with impaired liver function). In elderly patients and in patients with impaired liver function, concomitant use of cimetidine and venlafaxine should be carried out under medical supervision.

There was no clinically significant interaction of venlafaxine with antihypertensive (including beta-blockers, ACE inhibitors and diuretics) and hypoglycemic drugs.

Since the plasma protein binding of venlafaxine and EFA is 27% and 30%, respectively, no drug interaction is expected due to the competitive release of other drugs from plasma protein bonds.

Venlafaxine is metabolized by the cytochrome P450 system and the CYP2D6 and CYP3A4 isoenzymes. Taking the drug with inhibitors of the CYP2D6 isoenzyme or patients with a genetically determined decrease in the activity of the CYP2D6 isoenzyme was not accompanied by significant changes in the concentration of the Active ingredient and metabolite (venlafaxine and EFA), which allows not to reduce the dose of the antidepressant. However, concomitant use with inhibitors of the CYP3A4 isoenzyme is accompanied by an increase in the concentration of venlafaxine in plasma. Therefore, special care should be taken when prescribing venlafaxine with drugs that are inhibitors of the CYP3A4 isoenzyme (ketoconazole, erythromycin) or both isoenzymes (CYP2D6 and CYP3A4).

Venlafaxine is a relatively weak inhibitor of the CYP2D6 isoenzyme and does not inhibit the activity of the CYP1A2, CYP2C9, and CYP3A4 isoenzymes. In vivo studies did not reveal the effect of venlafaxine on the metabolism of alprazolam (CYP3A4 isoenzyme), caffeine (CYP1A2 isoenzyme), carbamazepine (CYP3A4 isoenzyme) and diazepam (CYP3A4 and CYP2C19 isoenzymes).

When used concomitantly with warfarin, the anticoagulant effect of the latter may increase, while the prothrombin time, expressed in MHO, is prolonged.

When administered concomitantly with indinavir, the AUC of indinavir decreased by 28% and its Cmax in plasma decreased by 36%, while the pharmacokinetic parameters of venlafaxine and EFA did not change. The clinical significance of this effect is unknown.

Venlafaxine may affect the pharmacodynamics of other drugs acting at the level of the serotonergic neurotransmitter system, so caution should be exercised when it is co-administered with triptans, other selective serotonin reuptake inhibitors and lithium preparations.

How to take, course of use and dosage

Pills Velafaxa is recommended to be taken orally, during meals, preferably at the same time, without chewing and washing down with liquid.

For the treatment of depression, the recommended starting dose is 37.5 mg 2 times / day daily. If after several weeks of treatment there is no significant improvement, the dose can be increased to 150 mg / day-75 mg 2 times / day.

If it is necessary to use the drug in a higher dose for severe depressive disorder or other conditions requiring inpatient treatment, you can immediately prescribe 75 mg 2 times a day. After that, the daily dose can be increased by 75 mg every 2-3 days until the desired therapeutic effect is achieved.

The maximum daily dose of Velafax is 375 mg. After achieving the necessary therapeutic effect, the daily dose can be gradually reduced to the minimum effective level. Maintenance therapy and relapse prevention continues for 6 months or more. The drug is prescribed at the minimum effective dose used in the treatment of a depressive episode.

Overdose

Symptoms (often occur when taking ethanol at the same time):dizziness, decreased blood pressure, ECG changes (QT interval prolongation, bundle branch block, QRS complex expansion), sinus and ventricular tachycardia or bradycardia, impaired consciousness (from drowsiness to coma), convulsions, death.

Treatment: conduct symptomatic therapy, under continuous monitoring of the ECG and the functions of vital organs. It is not recommended to induce vomiting due to the risk of aspiration. It is recommended to ensure airway patency, adequate pulmonary ventilation and oxygenation. Hemodialysis is ineffective because venlafaxine and EFA are not eliminated during dialysis. Specific antidotes are unknown.

Special instructions

Depression increases the risk of suicidal thoughts and attempts. This risk persists until persistent remission occurs. Since improvement may not occur within the first few weeks of treatment or more, patients should be under constant medical supervision throughout this period until a lasting improvement occurs. The risk of suicide attempts is highest immediately after starting the drug, but also increases again in the early stages of recovery, Velafax should not be used in the treatment of children and adolescents under 18 years of age. Patients with a history of suicidal behavior, or a tendency to develop suicidal thoughts before starting treatment, as well as young adult patients, have the highest risk of suicidal thoughts or suicide attempts. Placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders have shown an increased likelihood of suicidal behavior (suicide attempt and suicidal thoughts) in individuals under 25 years of age receiving antidepressants, including venlafaxine.

Patients and caregivers should be warned to monitor the occurrence of suicidal thoughts and seek immediate medical attention if appropriate symptoms occur.

As with other antidepressant medications, abrupt discontinuation of venlafaxine therapy – especially after high doses of the drug – may cause withdrawal symptoms, and it is recommended to gradually reduce the dose before discontinuing the drug. The risk of withdrawal symptoms depends on the dose, duration of therapy, and individual sensitivity of the patient. Patients with affective disorders who are treated with antidepressants (including venlafaxine) may experience hypomanic or manic states. Velafax (like other antidepressants) should be used with caution in patients with a history of mania (such patients need medical supervision).

Like other antidepressants, venlafaxine should be used with caution in patients with a history of epileptic seizures. Treatment with venlafaxine should be discontinued if epileptic seizures occur. The drug should not be prescribed to patients with uncontrolled epilepsy, and patients with controlled epilepsy should be closely monitored.

Venlafaxine use may be associated with the development of psychomotor restlessness, which is clinically akathisic and is characterized by subjectively unpleasant and distressing restlessness with a need to move, often combined with an inability to sit or stand still. This condition is most often seen during the first few weeks of treatment. If these symptoms occur, increasing the dose may have an adverse effect and consideration should be given to whether to continue taking venlafaxine.

Patients should be warned to seek immediate medical attention if they experience a rash, urticaria, or other allergic reaction.

In some patients, a dose-dependent increase in blood pressure was observed while taking venlafaxine, and therefore regular blood pressure monitoring is recommended, especially during the period of dose selection or increase.

Against the background of treatment with the drug, an increase in heart rate is possible, especially during use in high doses. Caution should be exercised when using the drug in patients with a tendency to tachycardia.

Patients, especially the elderly, should be warned about the possibility of dizziness and impaired sense of balance (orthostatic hypotension).

Changes in ECG parameters (PR interval prolongation, QRS complex extension, QT interval prolongation) were rarely observed in patients taking venlafaxine.

Venlafaxine should be used with caution in patients with recent myocardial infarction and unstable angina, as the safety of the drug in this category of patients has not been studied.

Like other serotonin reuptake inhibitors, venlafaxine may increase the risk of hemorrhage in the skin and mucous membranes. Caution should be exercised when treating patients predisposed to these conditions.

When taking venlafaxine, especially in conditions of dehydration or reduced circulating blood volume (including:elderly patients and patients taking diuretics) may experience hyponatremia and / or syndrome of insufficient secretion of antidiuretic hormone.

While taking the drug, mydriasis may occur, and therefore it is recommended to monitor intraocular pressure in patients who are prone to its increase or with angle-closure glaucoma.

It is not recommended to combine venlafaxine with drugs that reduce body weight (including phentermine), due to the lack of data on efficacy and safety.

Clinical studies conducted to date have not revealed tolerance to or dependence on venlafaxine. Despite this, the doctor should establish close monitoring of patients for signs of drug abuse (as with treatment with other drugs that affect the central nervous system). Patients with a history of drug dependence should be monitored closely.

When using venlafaxine for a long period of time, monitoring of serum cholesterol levels is required.

With caution, the drug should be prescribed in case of impaired liver or kidney function. Sometimes it may be necessary to reduce the dose.

When taking venlafaxine, special care should be taken when conducting electroconvulsive therapy, since there is no experience of using venlafaxine in these conditions.

During the treatment period, alcohol consumption is not recommended.

Influence on the ability to drive motor vehicles and manage mechanisms

Venlafaxine has almost no effect on psychomotor and cognitive functions. However, given the possibility of significant side effects from the central nervous system, during treatment with venlafaxine, care should be taken when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets are light yellow or yellow in color, round, with a dividing risk on one side and the inscription “PLIVA” on the other.

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Venlafaxine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets