Velaxin, sustained release capsules 150mg 28pcs

Composition

1 capsule of prolonged action contains:

Active ingredient:

venlafaxine hydrochloride 169.68 mg (equivalent to 150 mg of venlafaxine, respectively)

auxiliary substances:

MCC;

sodium chloride;

ethylcellulose;

talc;

dimethicone;

potassium chloride;

copovidone;

colloidal anhydrous silicon dioxide;

xanthan gum;

yellow iron oxide;

gelatin capsule:

titanium dioxide;

iron oxide red;

iron oxide yellow;

gelatin

Pharmacological action

Pharmacodynamics

The mechanism of the antidepressant effect of Velaxin is related to its ability to potentiate the transmission of nerve impulses in the central nervous system. Venlafaxine and its major metabolite O-desmethylvenlafaxine (EFA) are strong serotonin and norepinephrine reuptake inhibitors and weak dopamine reuptake inhibitors. Venlafaxine has no resistance to muscarinic, cholinergic, histamine (H1) and 1-adrenergic receptors of the brain.

Venlafaxine does not inhibit monoamine oxidase (MAO) activity. It has no affinity for opiate, benzodiazepine, phencyclidine or N-methyl-d-aspartate (NMDA) receptors.

Pharmacokinetics

After taking Velaxin long-acting capsules, _cmax of venlafaxine and EFA (the main metabolite) in plasma are reached within (6.0±1.5) and (8.8±2.2) hours, respectively. The rate of absorption of venlafaxine from long-acting capsules is lower than the rate of its elimination. Therefore, T_1/2 of venlafaxine after the appointment of Velaxin in the form of prolonged-acting capsules — (15±6) h-is actually T_1/2 of absorption, rather than T_1/2 of distribution — (5±2) h -, which is noted after the appointment of the drug Velaxin in the form of tablets.

The binding of venlafaxine and EFA to plasma proteins is 27 and 30%, respectively. EFA and other metabolites, as well as unmetabolized venlafaxine, are excreted by the kidneys. With repeated use of C_ss venlafaxine and EFA are achieved within 3 days. In the daily dose range of 75-450 mg, venlafaxine and EFA have linear kinetics. After taking the drug with a meal, Tmax in blood plasma increases by 20-30 minutes, but the values of_cmax and absorption do not change.

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, the total clearance of venlafaxine and EFA decreases, and T_1/2 increases. The decrease in total clearance is mainly observed in patients with creatinine clearance below 30 ml/min.

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

Indications

Depression of various etiologies, treatment and prevention

Use during pregnancy and lactation

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

Venlafaxine and EFA are excreted in breast milk. The safety of these substances for newborns has not been proven, so taking venlafaxine during breastfeeding is not recommended. If it is necessary to take the drug during lactation, the question of stopping breastfeeding should be decided. If the mother’s treatment was completed shortly before delivery, the newborn may experience withdrawal symptoms.

Contraindications

• hypersensitivity to any component of Velaxin;
• concomitant use of MAO inhibitors;
• severe renal and / or hepatic impairment (glomerular filtration rate (GFR) less than 10 ml / min, PV greater than 18 seconds);
• age under 18 years (safety and efficacy for this age group have not been proven);
• pregnancy or prospective pregnancy;
• lactation period (there are insufficient data from controlled studies).

With caution: recent myocardial infarction, unstable angina, heart failure, coronary artery disease, ECG changes, including prolongation of the QT interval, electrolyte balance disorders, arterial hypertension, tachycardia, convulsions in the anamnesis, intraocular hypertension, angle-closure glaucoma, manic conditions in the anamnesis, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight bodies.

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.

Common symptoms: weakness, fatigue.

From the gastrointestinal tract: decreased appetite, constipation, nausea, vomiting, dry mouth.

From the side of metabolism: increased serum cholesterol, reduced body weight.

From the cardiovascular system: arterial hypertension. hyperemia of the skin.

From the nervous system: unusual dreams, dizziness, insomnia, increased excitability, paresthesia, stupor, increased muscle tone, tremor, yawning.

From the genitourinary system: ejaculation disorders, erections, anorgasmia, dysuric disorders. Sensory disorders: accommodation disorders, mydriasis, visual impairment.

Skin disorders: sweating. After abrupt withdrawal of venlafaxine or reduction of its dose, the following symptoms may occur: fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, increased irritability, sweating. These symptoms are usually mild and go away without treatment. Because of the likelihood of these symptoms, it is very important to gradually reduce the dose of the drug.

Interaction

Concomitant use of MAO inhibitors and venlafaxine is contraindicated. Velaxin should be started at least 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 at least 7 days after discontinuation of Velaxin.

Concomitant use of venlafaxine with lithium may increase the level of the latter.

When co-administered with imipramine, the pharmacokinetics of venlafaxine and EFA do not change. At the same time, their simultaneous use increases the effects of desipramine — the main metabolite of imipramine — and its other metabolite,2 — OH-imipramine, although the clinical significance of this phenomenon is unknown.

Haloperidol: Co-use increases the level of haloperidol in the blood and enhances its effects.

The pharmacokinetics of drugs and their main metabolites do not change significantly when used concomitantly with diazepam. There was also no effect on the psychomotor and psychometric effects of diazepam.

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

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

The decrease in mental and motor activity under the influence of alcohol did not increase after taking venlafaxine. Despite this, as in the case of taking other drugs that affect the central nervous system, during therapy with venlafaxine, the use of alcoholic beverages is not recommended.

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

Drugs metabolized by cytochrome P450 isoenzymes: The cytochrome P450 CYP2D6 enzyme converts venlafaxine to the active metabolite of EFA. Unlike many other antidepressants, the dose of venlafaxine may not be reduced when administered concomitantly with drugs that inhibit CYP2D6 activity, or in patients with a genetically determined decrease in CYP2D6 activity, since the total concentration of venlafaxine and EFA will not change.

The main route of elimination of venlafaxine involves metabolism involving CYP2D6 and CYP3A4; therefore, special care should be taken when prescribing venlafaxine in combination with drugs that inhibit both of these enzymes. Such drug interactions have not yet been investigated.

Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not inhibit the activity of the CYP1A2, CYP2C9, and CYP3A4 isoenzymes; therefore, it should not be expected to interact with other drugs that are metabolized by these liver enzymes.

Cimetidine inhibits the first-pass metabolism of venlafaxine and has no effect on 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).

Clinical studies have not found clinically significant interactions of venlafaxine with antihypertensive (including beta-blockers, ACE inhibitors and diuretics) and antidiabetic drugs.

Plasma protein-bound drugs: Plasma protein binding is 27% for venlafaxine and 30% for EFA, so no drug interactions due to protein binding should be expected.

When taken concomitantly with warfarin, the anticoagulant effect of the latter may increase, while the PV lengthens and the MHO increases.

When co-administered with indinavir, the pharmacokinetics of indinavir change (with a 28% decrease in AUC and a 36% decrease in_cmax), and the pharmacokinetics of venlafaxine and EFA do not change. However, the clinical significance of this effect is unknown.

How to take, course of use and dosage

Inside, while eating. Each capsule should be swallowed whole and washed down with liquid. Capsules should not be divided, crushed, chewed, or placed in water. The daily dose should be taken in one dose (morning or evening), each time at approximately the same time.

Depression. The recommended starting dose is 75 mg once a day.

If the doctor thinks a higher dose is necessary (severe depressive disorder or other conditions requiring hospital treatment), you can immediately prescribe 150 mg once a day. Subsequently, the daily dose can be increased by 75 mg at intervals of 2 weeks or more (but not more often than after 4 days), until the desired therapeutic effect is achieved. The maximum daily dose is 350 mg.

After achieving the necessary therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

Maintenance therapy and relapse prevention. Treatment for depression should be continued for at least 6 months. In stabilizing therapy, as well as therapy to prevent relapses or new episodes of depression, doses that have been shown to be effective are usually used. The doctor should regularly (at least once every 3 months) monitor the effectiveness of long-term therapy with Velaxin.

Transfer of patients from Velaxin tablets. Patients taking the drug Velaxin in the form of tablets can be transferred to taking the drug in the form of capsules of prolonged action, with the appointment of an equivalent dose once a day. However, individual dose adjustments may be required.

Kidney failure. In patients with mild renal insufficiency (GFR greater than 30 ml / min), no dosage adjustment is required. In moderate renal insufficiency (GFR 10-30 ml / min), the dose should be reduced by 50%. Due to the prolongation of T_1/2 of venlafaxine and EFA, such patients should take the entire dose once a day. It is not recommended to use venlafaxine in patients with severe renal insufficiency (GFR less than 10 ml / min), since reliable data on such therapy are not available. Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completing hemodialysis.

Liver failure. In patients with mild hepatic insufficiency (PV less than 14 s), no dosage adjustment is required. In moderate hepatic insufficiency (PV from 14 to 18 s), the dose should be reduced by 50%. It is not recommended to use venlafaxine in patients with severe hepatic insufficiency, as reliable data on such therapy are not available.

Elderly patients. The patient’s advanced age alone does not require a dose adjustment, but (as with other medications) caution is required in the treatment of elderly patients, for example, due to the possibility of impaired renal function. The lowest effective dose should be used. If the dose is increased, the patient should be under close medical supervision.

Children and teenagers (under the age of 18). The safety and efficacy of venlafaxine in children and adolescents under 18 years of age have not been established.

Discontinuation of Velaxin. As with other antidepressant medications, abrupt discontinuation of venlafaxine (especially high doses) may cause withdrawal symptoms. Therefore, a gradual dose reduction is recommended before complete discontinuation of the drug. If high doses have been used for more than 6 weeks, it is recommended to reduce the dose for at least 2 weeks. The length of time required to reduce the dose depends on the amount of the dose, the duration of therapy, and the patient’s reactions.

Overdose

Symptoms: ECG changes (prolongation of the QT interval, bundle branch block, expansion of the QRS complex), sinus or ventricular tachycardia, bradycardia, hypotension, convulsions, depression of consciousness (decreased level of wakefulness). Venlafaxine overdose with concomitant use of alcohol and / or other psychotropic drugs has been reported to be fatal.

Treatment: symptomatic. Specific antidotes are unknown. Continuous monitoring of vital functions (respiration and blood circulation) is recommended. Use of activated charcoal to reduce the absorption of the drug. It is not recommended to induce vomiting due to the risk of aspiration. Venlafaxine and EFA are not eliminated by dialysis.

Special instructions

Depression increases the risk of suicidal thoughts and attempts. This risk persists until persistent remission occurs. Therefore, patients should be under constant medical supervision and given only a small number of capsules of the drug to reduce the risk of possible abuse and / or overdose.

Velaxin should not be used in the treatment of children and adolescents under 18 years of age. Increased likelihood of suicidal behavior (suicide attempt and suicidal thoughts), as well as hostility in clinical trials, is more often observed among children and adolescents receiving antidepressants compared to placebo groups.

Aggressive behavior has been reported while taking venlafaxine (especially at the beginning of treatment and after discontinuation of the drug).

The use of venlafaxine can cause psychomotor agitation, which is clinically similar to akathisia, characterized by restlessness with the need to move, often combined with the inability to sit or stand still. This is most often observed 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 the drug.

Like all antidepressants, venlafaxine should be used with caution in patients with a history of mania and/or hypomania, as the drug may cause an increase in their symptoms. In these cases, medical supervision is necessary.

Caution should be exercised when treating patients with a history of seizures. If convulsive seizures occur or their frequency increases, treatment with venlafaxine should be discontinued.

Similar to selective serotonin reuptake inhibitors, venlafaxine should be used with caution when used concomitantly with antipsychotic medications, as symptoms resembling neuroleptic malignant syndrome may develop.

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 at the beginning of the course of treatment or when increasing the dose.

Some cases of orthostatic hypotension have been reported while taking venlafaxine. Patients, especially the elderly, should be warned about the possibility of dizziness and impaired sense of balance.

Venlafaxine can cause an increase in your heart rate, especially when taking high doses. Special care should be taken when prescribing the drug to patients with conditions that may worsen with an increase in heart rate.

There have not been sufficient studies on the use of venlafaxine in patients who have recently had a myocardial infarction or suffer from decompensated heart failure, so this drug should be used with caution in these patients.

Like other serotonin reuptake inhibitors, venlafaxine can increase the risk of hemorrhage in the skin and mucous membranes, so caution is needed when treating patients who are predisposed to bleeding.

Hyponatremia and/or a syndrome of insufficient ADH secretion may occur while taking venlafaxine, especially in conditions of dehydration or reduced blood volume (including in elderly patients and patients taking diuretics).

Cases of mydriasis have been reported while taking venlafaxine, so patients with a predisposition to increased intraocular pressure or at risk of angle-closure glaucoma should be closely monitored.

Special care should be taken in patients with renal or hepatic insufficiency. In some cases, a dose reduction is required.

The safety and efficacy of venlafaxine with weight-reducing agents, including phentermine, have not been established, so their simultaneous use (as well as the use of venlafaxine as monotherapy for weight loss) is not recommended. Clinically significant increases in serum cholesterol were observed in some patients receiving venlafaxine for at least 4 months. Therefore, when taking the drug for a long time, it is advisable to monitor the level of serum cholesterol.

After discontinuation of the drug, especially sudden withdrawal symptoms often occur. The risk of withdrawal symptoms may depend on several factors, including the duration of the course and dose, as well as the rate of dose reduction. Withdrawal symptoms such as dizziness, sensory disturbances (including paresthesia and electric shock sensation), sleep disturbances (includinginsomnia and unusual dreams), agitation or anxiety, nausea and / or vomiting, tremors, sweating, headache, diarrhea, rapid and rapid heartbeat, and emotional instability are usually mild to moderate, but may be severe in some patients. They are usually observed in the first days after discontinuation of the drug, although there have been isolated reports of such symptoms in patients who accidentally missed a single dose. These symptoms usually resolve on their own within 2 weeks; however, in some patients they may be more prolonged (2-3 months or more). Therefore, before discontinuing venlafaxine, it is recommended to gradually reduce its dose over several weeks or months, depending on the patient’s condition.

Influence on the ability to drive a car or perform work that requires an increased rate of physical and mental reactions. It should be borne in mind that any drug therapy with psychoactive drugs can reduce the ability to make judgments, think or perform motor functions. The patient should be warned about this before starting treatment. If such effects occur, the extent and duration of restrictions should be determined by the doctor.

Form of production

Long-acting capsules

Storage conditions

Store in a dry place, at temperatures below 30°C.

Shelf

life is 5 years.

Active ingredient

Venlafaxine

Conditions of release from pharmacies

By prescription

Dosage form

long-acting capsules

Purpose

For adults as directed by your doctor

Indications

Depression