Velafax MV - instructions for use, dose, side effects, contraindications

insulating sheath: hypromellose (6cps) 6.00 mg or 12.00 mg, talc 2.00 mg or 4.00 mg; shell, regulating release of the active substance: (E-15) 0.90 mg or 1.80 mg, Surelise E-7-7050 (a complex component consisting of water, ethylcellulose (20 cf), 28% aqueous ammonia, dibutyl sebacate, acid, oily, colloidal silicon dioxide) 32.00 mg or 64.00 mg, talc 1.15 mg or 2.30 mg;

capsule shell: dye sunset yellow 0.0022 mg or 0.046 mg, dye quinoline yellow 0.2687 mg or 0.0225 mg, dye patented blue (for capsules 150 mg) 0.0006 mg, titanium dioxide 0.1047 mg or 1.6248 mg , sodium lauryl sulfate 0.08 mg or 0.08 mg, gelatin to 100 mg.

Description:

Capsules 75 mg. Hard gelatin capsules, size 1. The lid is yellow, the body is transparent. The contents of the capsules are pellets of white or almost white color.

Capsules 150 mg. Hard gelatin capsules, size 0. The cover is of a dark yellow color, the body is transparent. The contents of the capsules are pellets of white or almost white color.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Venlafaxine is an antidepressant. According to its chemical structure, it can not be assigned to any known class of antidepressants (tricyclic, tetracyclic or other).It has two active enantiomers.

Antidepressant effect Venlafaxine is associated with an increase in neurotransmitter activity in the central nervous system. Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA), are potent inhibitors of the reuptake of serotonin and norepinephrine and poorly inhibit the reuptake of dopamine by neurons. Venlafaxine and EFA are equally effective in reversing the capture of neurotransmitters. Venlafaxine and EFA have beta-adrenoblocking properties. Venlafaxine does not bind to m-cholino, H₁-gistamines and alpha₁-adrenoceptors of the brain. Venlafaxine does not suppress the activity of monoamine oxidase (MAO). Has no affinity for opioid, benzodiazepine, phencyclidine or N-methyl-d-Aspartate (NMDA) receptors.

Pharmacokinetics:

After receiving Velafax® MV capsule prolonged action, the maximum concentrations of venlafaxine and O-desmethylvenlafaxine (EFA basic metabolite) in plasma are reached within 6.0 ± 1.5 and 8.8 ± 2.2 hours, respectively. The rate of absorption of venlafaxine from prolonged-action capsules is lower than its elimination rate.Therefore, the half-life of venlafaxine after taking Velafax® MV capsule prolonged action (15 ± 6 hours) is, in fact, (T_1/2) suction than T_1/2distribution (5 ± 2 hours), which is noted after taking the drug Velafax ® tablets.

The binding of venlafaxine and EFA to plasma proteins is 27% and 30%, respectively. EFA and other metabolites, as well as nonmetabolized venlafaxine, are excreted by the kidneys. With repeated administration, the equilibrium concentrations of venlafaxine and EFA are reached within 3 days. In the range of daily doses of 75-450 mg, venlafaxine and EFA have linear kinetics. After taking the drug while eating, the time to reach the maximum concentration in the blood plasma increases by 20-30 minutes, but the maximum concentration and absorption do not change.

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

With moderate or severe renal failure the total clearance of venlafaxine and EFA is reduced, and the half-life is prolonged. The decrease in overall clearance is mainly observed in patients with creatinine clearance below 30 ml / min.

Age and sex of the patient do not affect the pharmacokinetics of the drug.

Indications:

Depression (including in the presence of anxiety), treatment and prevention of relapse.

Contraindications:

Hypersensitivity to any component of the drug.

Simultaneous administration of MAO inhibitors (see also section "Interaction").

Severe violations of kidney and / or liver function (GFR less than 10 ml / min, PV less than 18 sec).

Age to 18 years (safety and efficacy for this age group are not proven).

Pregnancy or presumptive pregnancy.

Lactation period (there is insufficient data from controlled trials).

Deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption.

Carefully:Recently suffered myocardial infarction, unstable angina, heart failure, coronary artery disease, ECG changes, including lengthening of the interval QT, abnormal electrolyte balance, arterial hypertension, tachycardia, history of convulsions, intraocular hypertension, closed angle glaucoma, manic conditions in the anamnesis, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight, with simultaneous diuretics, suicidal tendencies.

Pregnancy and lactation:

The safety of venlafaxine during pregnancy is not proven, therefore, use during pregnancy (or presumptive pregnancy) is possible only if the potential benefit to the mother exceeds the possible risk to the fetus. Women of childbearing age should be warned about this before starting treatment and should immediately seek medical attention in the event of pregnancy or planning pregnancy during drug treatment.

Venlafaxine and its metabolite (EFA) are excreted in breast milk. The safety of these substances for newborn babies is not proven, therefore, the use of venlafaxine during breastfeeding is not recommended. If you need to take the drug during lactation, you should decide whether to stop breastfeeding.

If the mother's treatment was completed shortly before the birth, a newborn can have withdrawal symptoms.

Dosing and Administration:

Velafax® MB long-acting capsules should be taken with meals. Each capsule should be swallowed whole and washed down with liquid. Capsules can not be divided, chopped, chewed or placed in water.The daily dose should be taken at one time (in the morning or in the evening) each time at approximately the same time.

Depression

The recommended initial dose is 75 mg once a day.

If, in the doctor's opinion, a higher dose is required (severe depressive disorder or other conditions requiring hospital treatment), 150 mg once a day can be immediately prescribed. Subsequently, the daily dose can be increased by 75 mg with an interval of two weeks or more (but no more than 4 days later), 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 a minimum effective level.

Supportive therapy and prevention of relapses

Treatment of depression should last at least 6 months. With stabilizing therapy, as well as therapy for the prevention of relapses or new episodes of depression, doses that demonstrate their effectiveness are usually used. The physician should regularly (at least once every 3 months) monitor the effectiveness of long-term therapy with Velafax® MB.

Transfer of patients from tablets Velafax®

Patients taking the preparation of Velafax® in a tablet dosage form can be transferred to receive Velafax® MB in the form of a sustained-release capsule with an equivalent dose once a day. However, an individual dose adjustment may be required.

Renal insufficiency: with mild renal insufficiency (glomerular filtration rate (GFR) of more than 30 ml / min), a correction mode is not required. With moderate renal failure (GFR 10-30 ml / min), the dose should be reduced by 50%. In connection with the lengthening of the half-life of venlafaxine and its active metabolite (EFA), such patients should take the entire dose once a day. It is not recommended to apply venlafaxine with severe renal failure (GFR less than 10 ml / min), because there are no reliable data on such therapy. Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completion of hemodialysis.

Liver failure: with mild hepatic insufficiency (prothrombin time (PV) less than 14 s) correction of the dosing regimen is not required.For moderate hepatic insufficiency, (IV 14 to 18 s), the dose should be reduced by 50%. It is not recommended to apply venlafaxine with severe hepatic insufficiency, since reliable data on such therapy are absent.

Elderly patients: the old age of the patient does not require a dose change, however, as with the prescription of other drugs, 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. When the dose is raised, the patient should be under careful medical supervision.

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

Abolition of Velafax® MB

As with the treatment with other antidepressants, abrupt withdrawal (especially high doses) of venlafaxine can cause withdrawal symptoms (see "Side effects" and "Special instructions" sections). Therefore, before the complete cancellation of the drug, a gradual dose reduction is recommended. If high doses have been used for more than 6 weeks, it is recommended to reduce doses for at least 2 weeks.The length of the period necessary to reduce the dose depends on the magnitude, dose, duration of therapy, and patient reactions.

Side effects:

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

In order of decreasing frequency: frequent (<1/10 and> 1/100); infrequent (<1/100 and> 1/1000); rare (<1/1000); very rare (<1/10000).

General symptoms: weakness, fatigue, headache, abdominal pain, chills, fever.

From the gastrointestinal tract: loss of appetite, constipation, nausea, vomiting, dry mouth; infrequent: grinding of teeth during sleep, reversible increase in activity of liver enzymes; rare: gastrointestinal bleeding; very rare: hepatitis, pancreatitis.

From the nervous system: dizziness, insomnia, agitation, drowsiness; frequent: unusual dreams, anxiety, confused state of consciousness, increased muscle tone, paresthesia, tremor; infrequent: apathy, hallucinations, myoclonus; rare: ataxia, speech disorders, including dysarthria, mania or hypomania (see p.section "Special instructions"), manifestations resembling neuroleptic malignant syndrome, convulsive seizures (see section "Special instructions"), serotonergic syndrome; extrapyramidal disorders, including dyskinesia and dystonia, akathisia (see section "Special instructions"); very rare: delirium.

From the side of the cardiovascular system: Arterial hypertension, widening of blood vessels (blood flow), heart palpitations; infrequent: orthostatic hypotension, syncope, arrhythmias (including tachycardia); Very rare: pirouette arrhythmia, lengthening of the interval QT, ventricular tachycardia, ventricular fibrillation.

From the sense organs: disorders of accommodation, mydriasis, impaired vision, tinnitus; infrequent: a violation of taste.

On the part of the hematopoiesis system: infrequent: hemorrhages in the skin (ecchymosis) and mucous membranes; rare: thrombocytopenia, prolonged bleeding time; very rare: agranulocytosis, aplastic anemia, neutropenia, pancytopenia.

From the skin; sweating, itching and rash; infrequent: reactions of photosensitivity, angioedema, macular-papular rashes,hives; rare: alopecia, erythema multiforme, Stevens-Johnson syndrome.

From the genitourinary system: violations of ejaculation, erection, orgasm, increased frequency of urination; infrequent: decreased libido, impotence, menstrual irregularity, menorrhagia, urinary retention; rare: galactorrhea.

From the side of metabolism: increased serum cholesterol levels (in some cases with prolonged use and, possibly, with high doses), increased or decreased body weight; infrequent: hyponatremia, syndrome of inadequate secretion of antidiuretic hormone; very rare: increased prolactin levels.

Musculoskeletal system: arthralgia, myalgia; infrequent: muscle spasm; very rare: rhabdomyolysis.

After a sharp abolition of venlafaxine or a decrease in its dose, fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, a feeling of faintness, diarrhea, insomnia, nightmares, anxiety, anxiety, disorientation, hypomania, weakness, impaired coordination, ringing in the ears, tremor, convulsions, paresthesia, sweating. These symptoms are usually mild and go untreated.Because of the likelihood of these symptoms, it is very important to gradually reduce the dose of the drug (like any other antidepressant), especially after taking high doses. The length of the period necessary to reduce the dose depends on the size of the dose, the duration of therapy, and the individual sensitivity of the patient.

Overdose:

Symptoms: ECG changes (lengthening interval QT, bundle branch blockade, expansion of the complex QRS), sinus or ventricular tachycardia, bradycardia, arterial hypotension, convulsive conditions, depression of consciousness, especially with an overdose of venlafaxine in combination with the use of alcohol or other psychotropic medications.

It was reported a lethal outcome with an overdose of venlafaxine while taking with alcohol and / or other psychotropic drugs.

Treatment: symptomatic. Specific antidotes are unknown. Provide adequate oxygenation and ventilation of the lungs. Continuous monitoring of heart rate and vital functions is recommended. The purpose of activated charcoal to reduce absorption of the drug. It is not recommended to induce vomiting due to the danger of aspiration. Venlafaxine and EFA are not derived from dialysis.

Interaction:

Simultaneous application monoamine oxidase inhibitors (MAO) and venlafaxine is contraindicated. The preparation of Velafax® MB can be started at least 14 days after the end of therapy with MAO inhibitors. Therapy with MAO inhibitors can begin at least 7 days after the withdrawal of Velafax® MB.

Serotonergic drugs: as theoretically possible interaction of venlafaxine with drugs that affect serotonin a neurotransmitter system (such as tryptans, selective serotonin reuptake inhibitors, or lithium), caution should be exercised when used simultaneously with these drugs.

The simultaneous use of venlafaxine with lithium does not affect the concentration of the latter.

When used simultaneously with imipramine / desipramine the pharmacokinetics of venlafaxine and its metabolite (EFA) does not change. At the same time, their simultaneous application intensifies. 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: combined use increases the concentration of haloperidol in the blood and enhances its effects.

When used simultaneously with diazepam Pharmacokinetics of drugs and their major metabolites do not change significantly. Also, there was no effect on the psychomotor and psychometric effects of diazepam.

When used simultaneously with clozapine there may be an increase in its concentration in the blood plasma and the development of side effects (eg, convulsive seizures).

When used simultaneously with risperidone (despite the increase AUC risperidone) the pharmacokinetics of the sum of active components (risperidone and its active metabolite) does not change significantly.

Reduction of mental and motor activity under the influence of alcohol did not increase after receiving venlafaxine. Despite this, as with other medications that affect the central nervous system, alcoholic beverages are not recommended during venlafaxine therapy.

On the background of taking venlafaxine, special care should be taken when electroconvulsive therapy, since there is no experience with venlafaxine under these conditions.

Drugs metabolized by cytochrome P450 isoenzymes:

Isozyme CYP2D6 system of cytochrome P450 converts venlafaxine in the active metabolite of EFA. Unlike many other antidepressants, the dose of venlafaxine can not be reduced with simultaneous administration with drugs, suppressing the activity of the isoenzyme CYP2D6, or in patients with a genetically caused decrease in the activity of the isoenzyme CYP2D6, since the total concentration of venlafaxine and EFA will not change at the same time.

The main way of removing venlafaxine involves metabolism with the participation of isoenzymes CYP2D6 and CYP3A4; therefore, special care should be taken with the appointment of venlafaxine in combination with drugs that depress both of these enzymes. Such drug interactions have not yet been investigated.

Venlafaxine is a relatively weak isoenzyme inhibitor CYP2D6 and does not suppress the activity of isoenzymes CYP1A2, CYP2C9 and CYP3A4; therefore, one should not expect its interaction with other drugs in the metabolism of which these microsomal enzymes of the liver participate.

Cimetidine suppresses the metabolism of the "first passage" of venlafaxine and does not affect the pharmacokinetics of EFA.In most patients, only a slight increase in the total pharmacological activity of venlafaxine and EFA is expected (but in elderly patients and with liver dysfunction, this is more pronounced and medical supervision is recommended).

With simultaneous reception with warfarin can increase the anticoagulant effect of the latter, while prolonging prothrombin time and increasing INR.

With simultaneous reception with indinavir the pharmacokinetics of indinavir (with a 28% decrease AUC and a 36% decrease in C_m_Oh), and the pharmacokinetics of venlafaxine and EFA do not change. However, the clinical significance of this effect is unknown.

Special instructions:

With depression, the risk of suicidal thoughts and suicidal attempts increases. This risk persists until a stable remission occurs. Therefore patients should be under constant medical supervision and they should give out only a small amount of capsules of the drug in order to reduce the risk of possible abuse and / or overdose.

Venlafaxine should not be used in the treatment of children and adolescents under the age of 18 years. Increased likelihood of suicidal behavior (attempted suicide and suicidal thoughts),as well as hostility, is more common in clinical trials among children and adolescents receiving antidepressants than in groups receiving placebo.

It was reported of aggressive behavior during the use of venlafaxine (especially at the beginning of the course of treatment and after drug withdrawal).

The use of venlafaxine can cause psychomotor agitation, which clinically resembles akathisia, is characterized by anxiety with the need to move, often in combination 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 it is advisable to continue taking the drug.

Like all antidepressants, venlafaxine should be administered with caution to a patient with a mania and / or hypomania in an anamnesis, since the drug may cause an increase in their signs. In these cases, medical supervision is necessary.

Care should be taken when treating patients with seizures in the anamnesis. If seizures occur or their frequency increases, treatment with venlafaxineshould be interrupted.

Like selective serotonin reuptake inhibitors, venlafaxine should be used with caution when used simultaneously with antipsychotic drugs, since symptoms resembling neuroleptic malignant syndrome may develop.

Patients should be warned of the need to consult a doctor immediately if rashes, hives, or other allergic reactions occur.

In some patients, when taking venlafaxine, a dose-dependent increase in blood pressure is noted, and therefore regular monitoring of blood pressure is recommended, especially at the beginning of the course of treatment or with increasing doses.

When taking venlafaxine, some cases of orthostatic hypotension are described. Patients, especially the elderly, should be warned about the possibility of dizziness and discomfort.

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

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

Like other serotonin reuptake inhibitors, venlafaxine may increase the risk of hemorrhages in the skin and mucous membranes, therefore, in the treatment of patients prone to bleeding, caution is necessary.

During the administration of venlafaxine, especially in conditions of dehydration or a decrease in blood volume (including elderly patients and patients taking diuretics), hyponatremia and / or a syndrome of insufficient secretion of antidiuretic hormoneSIADH).

During the reception of venlafaxine, cases of mydriasis are noted, so patients with a predisposition to increase intraocular pressure or who have a risk of angle-closure glaucoma need careful medical supervision.

With renal and hepatic insufficiency, special care is needed. In some cases, a dose reduction is required (see section "Method of administration and dose").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 a monotherapy to reduce body weight) is not recommended.

A clinically significant increase in serum cholesterol levels was observed in some patients receiving venlafaxine for at least 4 months. Therefore, with prolonged use of the drug, it is advisable to monitor the serum cholesterol level.

After discontinuation of the drug, especially sudden, often symptoms of withdrawal (see section "Side effect"). 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.

Symptoms of withdrawal include: dizziness, sensory disturbances (including paresthesia and sensations of electrical current), sleep disorders (including insomnia and unusual dreams), agitation or anxiety, nausea and / or vomiting, tremor, sweating, headache, diarrhea, rapid heartbeat and emotional instability, usually have a small or medium severity, but in some patients they can be severe.They are usually observed in the first days after the drug was discontinued, although there were isolated reports of the occurrence of such symptoms in patients who accidentally missed a single dose. Usually these phenomena pass independently for 2 weeks; However, in some patients they may be longer (2-3 months or more). Therefore venlafaxine before canceling it is recommended to progressively reduce the dose for several weeks or months depending upon the patient's condition (see. The sections "Dosage and Administration").

Effect on the ability to drive transp. cf. and fur:

It should be borne in mind that any drug therapy with psychoactive drugs can reduce the ability to make judgments, thinking or performing motor functions. This should be warned by the patient before starting treatment. If such effects occur, the extent and duration of the restrictions should be determined by the physician.

Form release / dosage:

Capsules of prolonged action.

Packaging:

For 10 capsules prolonged action in a blister of PVC / aluminum foil.

3 blisters with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007156/08

Date of registration:09.09.2008 / 15.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

CIPLA, Ltd. India

Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo

Information update date: & nbsp24.01.2017

Illustrated instructions

Instructions

Velafax® MB (Velafax® SR)