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

Excipients: microcrystalline cellulose, starch corn, iron dye oxide yellow (E 172), sodium carboxymethyl starch, talc, silicon dioxide colloid, magnesium stearate.

Description:

Dosage: 37.5 mg: oblong tablets of light yellow or yellow with a delicate risk on both sides.

Dosage of 75 mg: round tablets of light yellow or yellow color with a dividing risk on one side and engraving "PLIVA" on the other side.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Antidepressant, according to the chemical structure is not related to any known class of antidepressants (tricyclic, tetracyclic or other). It is a racemate of two active enantiomers. The antidepressant effect of venlafaxine is associated with the ability to potentiate the transmission of a nerve impulse in the CNS. Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA) are potent serotonin reuptake inhibitors and norepinephrine neurons and weakly inhibit the reuptake of dopamine. Venlafaxine and EFA reduce beta-adrenergic reactivity of the CNS both after a single dose and with constant admission.

Venlafaxine does not have an affinity for m-cholinergic, H₁-gistamine and α₁-adrenergic receptors of the brain.Does not suppress MAO activity. The drug does not affect the release of noradrenaline from the brain tissue.

Pharmacokinetics:

After oral administration venlafaxine is well absorbed from the digestive tract. After a single dose in doses of 25-150 mg, the maximum concentrations (FROM_m_Oh) in the blood plasma are achieved within approximately 2.4 hours and are 33-172 ng / ml. After taking the drug during meals, the time to reach the maximum concentration in the blood plasma is increased by 20-30 minutes, but the maximum concentration and absorption do not change.

Venlafaxine undergoes intensive metabolism during "first passage" through the liver. The main metabolite is O-desmethylvenlafaxine (EFA). The maximum concentration of EFA in blood plasma is reached approximately 4.3 hours after administration and is 61-325 ng / ml. In the range of daily doses of 75-450 mg, the pharmacokinetics of venlafaxine and EFA are linear.

The binding of venlafaxine and EFA to plasma proteins is 27% and 30%, respectively. With repeated intake, the equilibrium concentrations (C_ss) venlafaxine and EFA are achieved within 3 days.

The half-life (T_1/2) venlafaxine and EFA are 5 and 11 hours EFA and other metabolites, as well as unchanged venlafaxine, are excreted by the kidneys.

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 and severe renal failure (clearance of creatinine (CC) less than 30 ml / min), the total clearance of venlafaxine and EFA is reduced, and the half-life is increased.

Age and gender patient does not affect the pharmacokinetics of the drug.

Indications:

Treatment of depression of various etiologies, including depression, accompanied by symptoms of anxiety.

Contraindications:

- Individual intolerance of venlafaxine and other components of the drug;

- simultaneous administration of MAO inhibitors (see section "Interaction with other drugs");

- age up to 18 years;

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

- pregnancy and lactation.

Carefully:

Recently suffered myocardial infarction, unstable angina, arterial hypertension, tachycardia, a history of convulsive syndrome, increased intraocular pressure, angle-closure glaucoma, a history of manic history, hyponatremia, hypovolemia, dehydration, simultaneous intake of diuretics,suicidal tendencies, a predisposition to bleeding from the skin and mucous membranes, with initially reduced body weight.

Pregnancy and lactation:

During pregnancy (including before birth) venlafaxine contraindicated because the safety of its use in this period is not defined.

Venlafaxine and the metabolite of EFA are excreted in breast milk. The safety of these substances for newborn babies is not proven, so if necessary, taking the drug during lactation should stop breastfeeding for the duration of treatment.

Dosing and Administration:

Velafax ® tablets are taken orally, during meals, preferably at the same time, without chewing and washing with liquid.

For the treatment of depression the recommended initial dose of Velafax ® is 37.5 mg 2 times daily. If after several weeks of treatment there is no significant improvement, the dose can be increased to 150 mg per day - 75 mg twice a day.

If it is necessary to use the drug at a higher dose in severe depressive disorder or other conditions requiring in-patient treatment, 75 mg twice a day can be immediately prescribed.After this, 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 a minimum effective level.

Supportive treatment lasts for 6 months or more. The drug is prescribed in the minimum effective dose used in the treatment of a depressive episode.

With mild renal insufficiency (glomerular filtration rate more than 30 ml / min) correction of the dosing regimen is not required. With renal failure of moderate severity (glomerular filtration rate 10-30 ml / min), the dose should be reduced by 25-50%. In connection with the lengthening of the half-life of venlafaxine and its active metabolite (EFA), such patients should take the entire dose 1 time per day. With renal failure severe (glomerular filtration rate less than 10 ml / min), Velafax ® is not recommended, since the experience of such therapy is limited. Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completion of hemodialysis.

With mild hepatic impairment (prothrombin time (PV) less than 14 seconds) correction of the dosing regimen is not required. With moderate hepatic impairment (IV 14 to 18 sec), the dose should be reduced by 50%. In severe hepatic impairment The use of Velafax® is not recommended, since the experience of such therapy is limited.

To patients of advanced age correction of the dose is not required, however (as with the appointment of other drugs), care needs to be taken with caution, for example, in connection with the possibility of impaired renal function. Therefore, in elderly patients, the lowest effective dose of the drug should be used; If you need to increase the dose shown by careful medical supervision.

Termination of Velabax medication®: at the end of treatment, the dose is recommended to be reduced gradually. When applied at a dose equal to or exceeding 75 mg, with a course of 7 days or more, the drug is canceled for at least a week, gradually reducing the dose. When used in high doses for more than 6 weeks, the period required to completely stop the drug is at least 2 weeks. The appearance of symptoms of recurrence of the disease during the period of cancellationVelafax® requires the administration of the initial dose of the drug or a more gradual and prolonged reduction.

Side effects:

Side effects are classified according to the following frequency:

very often - not less than 10%;

often - not less than 1%, but less than 10%;

infrequently - not less than 0,1%, but less than 1%;

rarely - not less than 0.01%, but less than 0.1%;

very rarely - less than 0.01%, including isolated cases.

Most of the side effects listed below depend on the dose. With long-term treatment, their severity and frequency decrease, and the need for cancellation of therapy usually does not arise.

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

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

From the cardiovascular system: often - increased blood pressure, hyperemia of the skin; infrequently - lowering blood pressure, postural hypotension, syncope, arrhythmia, tachycardia; very rarely - arrhythmia of the type "pirouette", lengthening of the interval QT, ventricular tachycardia, ventricular fibrillation.

From the central and peripheral nervous system: often - dizziness, asthenia, nightmarish dreams, weakness, dizziness, insomnia, drowsiness, increased nervous excitability, paresthesia, stupor, hypertension of muscles, tremor, yawning, sedation; infrequently - apathy, hallucinations, myoclonus, syncope; rarely - convulsions, ataxia with imbalance and coordination of movement, speech impairment, mania or hypomania, serotonin syndrome, symptoms resembling malignant neuroleptic syndrome, epileptic seizures; in some cases - delirium, extrapyramidal disorders, incl. dyskinesia and dystonia, tardive dyskinesia, psychomotor anxiety / akathisia.

From the mental status: the frequency is unsettled - depression, the appearance of suicidal thoughts and suicidal behavior during therapy and after drug withdrawal.

On the part of the hematopoiesis and lymphatic system: infrequently - hemorrhages in the skin (ecchymosis) and mucous membranes, thrombocytopenia, lengthening bleeding time, hemorrhagic syndrome; in some cases - agranulocytosis, aplastic anemia, neutropenia and pancytopenia.

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

On the part of the reproductive system: often - decreased libido, erectile dysfunction and / or ejaculation, anorgasmia in men, menorrhagia; infrequently - a violation of the menstrual cycle, anorgasmia in women.

From the sense organs: often - disorders of accommodation, mydriasis, visual impairment, noise or ringing in ash; infrequently - a violation of taste.

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

From the respiratory system: infrequently - shortness of breath; in some cases - pulmonary eosinophilia.

From the endocrine system: rarely - galactorrhea; in some cases - an increase in the level of prolactin.

Allergic reactions: infrequently - skin rash (including maculopapular), itching, photosensitivity, angioedema,hives; rarely - multiforme exudative erythema, Stevens-Johnson syndrome; in some cases - anaphylactic reactions.

From the side of the musculoskeletal system: often - arthralgia, myalgia; infrequently - muscle spasms; in some cases - rhabdomyolysis.

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

Overdose:

Symptoms (often occur with simultaneous intake of ethanol): dizziness, lowering blood pressure, changes in ECG (lengthening interval QT, Block blocking the bundle of the bundle, expansion of the complex QRS), sinus and ventricular tachycardia or bradycardia, impaired consciousness (from drowsiness to coma), convulsions, death.

Treatment symptomatic, under the continuous control of ECG and the functions of vital organs. It is not recommended to induce vomiting due to the danger of aspiration. It is recommended to provide airway patency, adequate pulmonary ventilation and oxygenation. Hemodialysis is ineffective - venlafaxine and EFA are not derived from dialysis. Specific antidotes are unknown.

Interaction:

Simultaneous application MAO inhibitors and venlafaxine is contraindicated. Taking venlafaxine can begin no earlier than 14 days after the end of therapy with MAO inhibitors. If a reversible MAO inhibitor was used (moclobemide), this interval may be shorter (24 h). Therapy with MAO inhibitors can be started no earlier than 7 days after the cancellation of venlafaxine.

With the simultaneous use of venlafaxine with lithium preparations it is possible to increase the level of lithium in the blood.

When used simultaneously with imipramine the pharmacokinetics of venlafaxine and its metabolite EFA does not change. Venlafaxine does not affect the metabolism of imipramine and its metabolite 2-hydroxyimipramine, but it increases the area under the pharmacokinetic curve and the maximum plasma concentrations of desipramine (the main metabolite of imipramine), and also reduces the renal clearance of 2-hydroxydesipramine. The clinical significance of this phenomenon is unknown.

With simultaneous use with neuroleptics, the appearance of symptoms resembling a malignant neuroleptic syndrome is possible.

Venlafaxine on 42% reduces renal clearance haloperidol, with the area under the pharmacokinetic curve and FROM_max increase by 70% and 88% respectively. It is possible to enhance the effects of haloperidol.

When used simultaneously with diazepam Pharmacokinetics of drugs and their major metabolites does not change significantly.

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

When used simultaneously with risperidone, despite the increase in the area under the pharmacokinetic curve of the drug, the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) did not change significantly.

Simultaneous reception ethanol and venlafaxine was not accompanied by a decrease in mental and motor activity. Despite this (as in the case of taking other drugs that affect the central nervous system) during the treatment with venlafaxine, ethanol is not recommended.

Cimetidine suppresses the metabolism of venlafaxine in 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 liver failure). In elderly patients and patients with impaired liver function, simultaneous use of cimetidine and venlafaxine should be performed under medical supervision.

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

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

The metabolism of venlafaxine occurs with the participation of the cytochrome P450 system, isoenzymes CYP2D6 and CYP3A4. Taking the drug with inhibitors of the isoenzyme CYP2D6 or patients with a genetically determined decrease in isoenzyme activity CYP2D6 no significant changes in the concentration of active substance and metabolite (venlafaxine and EFA), which does not reduce the dose of antidepressant. However, simultaneous administration with isoenzyme inhibitors CYP3A4 is accompanied by an increase in the concentration of venlafaxine in the plasma. Therefore, special care should be taken with the appointment of venlafaxine with drugs that are inhibitors of the isoenzyme CYP3A4 (ketoconazole, erythromycin) or both isoenzymes (CYP2D6 and CYP3A4).

Venlafaxine is a relatively weak isoenzyme inhibitor CYP2D6 and does not suppress the activity of isoenzymes CYP1A2, CYP2C9 and CYP3A4. In studies in vivo no effect of venlafaxine on alprazolam metabolism (isozyme CYP3A4), caffeine (isoenzyme CYP1A2), carbamazepine (isoenzyme CYP3A4) and diazepam (isozymes CYP3A4 and CYP2C19).

When used simultaneously with warfarin it is possible to increase the anticoagulant effect of the latter, while the prothrombin time, expressed through INR (the international normalized ratio), is prolonged.

With simultaneous reception with indinavir the area under the pharmacokinetic curve of indinavir is reduced by 28% and its maximum plasma concentration is reduced by 36%, while the pharmacokinetic parameters of venlafaxine and EFA do 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, therefore caution should be exercised when it is administered simultaneously with tryptanes, other selective serotonin reuptake inhibitors, and lithium preparations.

Special instructions:

With depression, the risk of suicidal thoughts and suicidal attempts increases. This risk persists until a stable remission occurs. Because the improvement may not occur within the first few weeks of treatment or more, patients should be under constant medical supervision throughout this period until the onset of a persistent improvement.The risk of suicidal attempts is highest immediately after starting the drug, but it also rises again in the early stages of recovery. Venlafaxine should not be used in the treatment of children and adolescents under the age of 18 years. In patients with a history of suicidal behavior or propensity to occurrence of suicidal thoughts prior to treatment, as well as in adults younger patients, the risk of suicidal thoughts or suicide attempts was highest. In placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased likelihood of suicidal behavior (suicide attempt and suicidal thoughts) in individuals under 25 years of age receiving antidepressants, including venlafaxine. Patients and people caring for patients should be warned about the need to monitor the appearance of suicidal thoughts and immediately seek medical help if symptoms appear.

As with the treatment with other antidepressants, a sharp discontinuation of venlafaxine therapy - especially after high doses of the drug - can cause symptoms of the "withdrawal" syndrome, and therefore it is recommended that before taking the drug, gradually reduce its dose.The risk of the symptoms of the "withdrawal" syndrome depends on the size of the dose, the duration of therapy, and the individual sensitivity of the patient. In patients with affective disorders in the treatment of antidepressants (including venlafaxine), hypomanic or manic conditions may occur. Venlafaxine (like other antidepressants) should be administered with caution to patients with a history of mania (such patients need medical supervision).

Like other antidepressants, venlafaxine should be administered with caution to patients with epileptic seizures in the anamnesis. Treatment with venlafaxine should be interrupted if epileptic seizures occur. The drug should not be given to patients with uncontrolled epilepsy, and patients with controlled epilepsy need careful monitoring.

The use of venlafaxine can be associated with the development of psychomotor anxiety, which clinically resembles akathisia and is characterized by subjectively unpleasant and distressing anxiety with the need to move, often in combination with the inability to sit or stand still.This condition is most often observed during the first few weeks of treatment. If such 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 of the need to consult a doctor immediately if rashes, hives, or other allergic reactions occur.

In some patients, when taking venlafaxine, a dose-related increase in blood pressure is noted, therefore regular monitoring of blood pressure is recommended, especially during the period of selection or increase of the dose.

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

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

In patients receiving venlafaxine, changes in ECG parameters were rarely observed (lengthening of the interval PR, expansion of the complex QRS, interval lengthening QT).

Caution should be given venlafaxine patients who have recently undergone a myocardial infarction and with unstable angina because 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 hemorrhages in the skin and mucous membranes. Care should be taken when treating patients who are predisposed to such conditions.

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

During the administration of the drug may be observed mydriasis, in connection with which it is recommended to control intraocular pressure in patients prone to its increase or with a closed-angle glaucoma.

It is not recommended to combine venlafaxine with funds that reduce body weight (including phentermine), due to lack of data on efficacy and safety. Clinical studies conducted to date have not revealed a tolerance to or dependence on venlafaxine.Despite this, the physician should establish close monitoring of patients to identify signs of drug abuse (as with other drugs acting on the central nervous system). In special control, patients who have a history of drug dependence are in need.

When using venlafaxine for a long period of time requires monitoring serum cholesterol levels.

With caution should prescribe the drug in violation of the liver or kidneys. Sometimes a dose reduction may be required.

On the background of taking venlafaxine, special care should be taken when conducting electroconvulsive therapy, experience with venlafaxine in these conditions is absent.

During the treatment is not recommended the use of alcohol.

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

Venlafaxine practically does not affect psychomotor and cognitive functions. However, given the possibility of significant side effects from the central nervous system, during treatment with venlafaxine, care must be taken when driving vehicles and engaging in potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets, 37.5 mg and 75 mg.

Packaging:

For 14 tablets are placed in a blister of PVC film and aluminum foil.

For 2 or 4 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 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:LS-000676

Date of registration:23.07.2010

Expiration Date:Unlimited

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

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo

Information update date: & nbsp24.01.2017

Illustrated instructions

Instructions

Velafax® (Velafax®)