Epevelone retard - instructions for use, dose, side effects, contraindications

Excipients: silicon colloid dioxide 1.51 mg, magnesium stearate 5712 5, mg, calcium hydrophosphate dihydrate 16 mg, kollidone SR (polyvinyl acetate 102.46 mg, povidone 24.33 mg, silicon dioxide colloid 0.256 mg, sodium lauryl sulfate 1.025 mg);

shell: macrogol 6000 1.9%, titanium dioxide 2.21%, talc 4.42%; ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate copolymer (1: 2: 0.1) (Eudragit Rs30) 53%.

1 tablet 75 mg contains:

active substance: venlafaxine hydrochloride corresponding to 75 mg of venlafaxine;

Excipients: silicon colloid dioxide 3,02 mg, magnesium stearate 5712 10 mg, calcium hydrophosphate dihydrate 32 mg, kollidone SR (polyvinyl acetate 204.91 mg, povidone 48.67 mg, silicon dioxide colloid 0.512 mg, sodium lauryl sulfate 2,049 mg);

shell: macrogol 6000 1.9%, titanium dioxide 2.21%, talc 4.42%; ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate copolymer (1: 2: 0.1) (Eudragit Rs30) 53%.

1 tablet of 150 mg contains:

active substance: venlafaxine hydrochloride corresponding to 150 mg of venlafaxine;

Excipients: silicon dioxide colloid 6.04 mg, magnesium stearate 5712 20 mg, calcium hydrophosphate dihydrate 64 mg, kollidone SR (polyvinyl acetate 409.82 mg, povidone 97.34 mg, silicon dioxide colloid 1.024 mg, sodium lauryl sulfate 4.098 mg);

shell: macrogol 6000 1.9%, titanium dioxide 2.21%, talc 4.42%; ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate copolymer (1: 2: 0.1) (Eudragit Rs30) 53%.

Description:

Tablets 37.5 mg: round, biconvex tablets, covered with a film shell of white or almost white color with engraving V3 one side. On the fracture, the core is white or almost white, covered with a continuous layer of white shell.

Tablets 75 mg: round, biconvex tablets, covered with a film shell of white or almost white color with engraving V4 one side. On the fracture, the core is white or almost white, covered with a continuous layer of white shell.

Tablets of 150 mg: oval, biconvex tablets, covered with a film shell of white or almost white with an engraving V5 one side. On the fracture, the core is white or almost white, covered with a continuous layer of white shell.

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 enantiomeric racemic forms.

The antidepressant effect of 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 reduce beta-adrenergic reactions.

Venlafaxine does not have an affinity for muscarinic, cholinergic, histamine (H₁) and α₁-adrenergic receptors of the brain. Venlafaxine does not suppress the activity of monoamine oxidase (MAO). Has no affinity for opiate, benzodiazepine, phencyclidine or N-methyl-d-Aspartate (NMDA) receptors.

Pharmacokinetics:

The absolute bioavailability of venlafaxine after oral administration is 42% ± 15%.

The maximum plasma concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine (EFA) are reached after 6 and 9 hours, respectively. The half-life of venlafaxine (T_1/2) - 15 hours. The connection with the proteins of the blood plasma of venlafaxine and its main metabolite is 27% and 30%, respectively. Venlafaxine extensively metabolism in the liver, mainly with the participation of isoenzyme CYP2D6, up to the main metabolite - EFA. Venlafaxine also metabolized to N-desmethylvenlafaxine, mainly with the participation of isoenzyme CYP3A3/4. Venlafaxine, EFA and other metabolites are excreted by the kidneys. About 87% of the dose is excreted in the urine 48 hours after taking 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 renal and / or hepatic impairment (glomerular filtration rate (GFR) is less than 10 ml / min, prothrombin time (PT) is more 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).

Carefully:

Recently suffered myocardial infarction, unstable angina, hypertension, tachycardia, history of convulsions, intraocular hypertension, angle-closure glaucoma,manic conditions in the anamnesis, hyponatremia, hypovolemia, dehydration, simultaneous reception of diuretics, suicidal tendencies, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight, renal / hepatic insufficiency.

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 infants 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:

EEPHELON retard should be taken orally, without chewing, while eating. Each tablet should be washed down with liquid. The daily dose should be taken at one time (in the morning or in the evening) each time approximately at 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 at intervals 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 doctor should regularly (at least once every 3 months) monitor the effectiveness of prolonged therapy with the drug EFEVELON retard.

Renal insufficiency: with mild renal failure (glomerular filtration rate (GFR) more than 30 ml / min) correction of the dosing regimen is not required. With GFR 10-30 ml / min, the dose should be reduced by 50%. 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 (PV less than 14 sec) correction of the dosing regimen is not required. With moderate hepatic insufficiency (IV 14 to 18 sec), 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 medications, caution is needed 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.

Removal of the drug EFEVELON retard

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

Common symptoms: weakness, increased fatigue.

From the gastrointestinal tract: frequent - decreased appetite, constipation, nausea, vomiting, dry mouth; infrequent - bruxism, reversible increase in the activity of "liver" transaminases; rare - hepatitis.

From the nervous system: frequent - dizziness, asthenia, insomnia, unusual dreams, increased nervous excitability, anxiety, stupor, increased muscle tone, paresthesia, tremor, sedation; infrequent, - apathy, hallucinations, myoclonus, syncope, muscle spasms, serotonergic syndrome; rare - mania or hypomania (see section "Special instructions"), manifestations resembling malignant neuroleptic syndrome, epileptic seizures (see section "Special instructions").

From the cardiovascular system: frequent - arterial hypertension, hyperemia of the skin; infrequent - lowering of arterial pressure, postural hypotension, tachycardia; very rare - lengthening interval QT, ventricular fibrillation, ventricular tachycardia (including ventricular fibrillation).

On the part of organs feelings: frequent - a violation of accommodation, mydriasis, impaired vision; infrequent - a violation of taste.

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

From the skin: sweating.

Allergic reactions: infrequent - rash, photosensitivity; very rare - multiforme exudative erythema (including Stevens-Johnson syndrome), anaphylaxis.

From the genitourinary system: violation of ejaculation, erections, anorgasmia, dysuric disorders (mainly - difficulty in the beginning of urination); infrequent - decreased libido, menorrhagia, urinary retention, violation of orgasm in women.

From the side of metabolism: increase serum cholesterol levels; infrequent - hyponatremia, syndrome of inadequate secretion of antidiuretic hormone.

Other: frequent - hyperperspiration (including night), weight loss; infrequent - increase in body weight.

After severe cancellation of venlafaxine or a decrease in its dose, fatigue, sleep disturbances (change in the nature of dreams, drowsiness or insomnia, difficulty falling asleep), headache, asthenia, nausea, vomiting, decreased appetite,dry mouth, dizziness, diarrhea, anxiety, hypomania, increased nervous excitability, confusion, 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, especially after taking high doses.

Overdose:

Symptoms: changes on ECG (lengthening interval QT, blockade of the legs of the bundle, enlargement of the complex QRS), dizziness, sinus or ventricular tachycardia, bradycardia, arterial hypotension, convulsive conditions, altered consciousness (decreased wakefulness). In case of an overdose of venlafaxine with simultaneous reception with alcohol and / or other psychotropic drugs, a lethal outcome was reported.

Treatment: symptomatic. Specific antidotes are unknown. Recommended continuous monitoring of vital functions (breathing and circulation). 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 it is contraindicated. You can start taking Ephevelone retard with at least 14 days after the end of therapy with MAO inhibitors. If a reversible MAO inhibitor was used (moclobemide), this interval can be shorter (24 hours). Therapy with MAO inhibitors can begin at least 7 days after the withdrawal of the drug EFEVELON retard.

Venlafaxine does not affect the pharmacokinetics lithium.

When used simultaneously with imipramine the pharmacokinetics of venlafaxine and its metabolite (EFA) will not change. Also, the joint administration does not affect the pharmacokinetics imipramine and 2-OH-imipramine, however, the total renal clearance of 2-OH-desipramine decreases, and the indices AUC and C_m_Oh desipramine increase by 35%.

Joint application with haloperidol increases its level in the blood and strengthens 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 level in the blood plasma and developmentside 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.

Increases the effect of ethanol on psychomotor reactions. 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 in these conditions.

Drugs metabolized by cytochrome P450 isoenzymes:

Enzyme CYP2D6 system of cytochrome P450 converts venlafaxine in the active metabolite of EFA. In contrast to many other antidepressants, the dose of venlafaxine can not be reduced with simultaneous administration with drugs that suppress activity CYP2D6, or in patients with a genetically determined decrease in activity CYP2D6, since the total concentration of venlafaxine and EFA does not change in this case.

The main way of removing venlafaxine involves metabolism involving 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 inhibitor CYP2D6 and does not suppress the activity of isoenzymes CYP1A2, CYP2C9 and CYP3A4; therefore, its interaction with other drugs in the metabolism of which these hepatic enzymes are involved should not be expected.

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 overall pharmacological activity of venlafaxine and EFA is expected (more pronounced in elderly patients and in liver failure).

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

Drugs associated with blood plasma proteins: binding to plasma proteins is 27% for venlafaxine and 30% for EFA, so venlafaxine does not affect the concentration of drugs in the blood plasma, which have a high degree of binding to proteins.

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:

The appointment of venlafaxine is possible no earlier than 14 days after discontinuation of therapy with MAO inhibitors and should be discontinued no less than 7 days prior to the commencement of taking any MAO inhibitor (dizziness, nausea, vomiting, hyperpersia, skin flushing, tremor, myoclonus, hyperthermia, signs similar to malignant neuroleptic syndrome, seizures, up to fatal outcome).

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 tablets of the drug in order to reduce the risk of possible abuse and / or overdose. Ephevel retard should not be used in the treatment of children and adolescents under the age of 18. An increase in the likelihood of suicidal behavior (suicide attempt and suicidal ideation), as well as hostility, is more common in clinical trials among children and adolescents receiving antidepressants than in groups receiving a 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).

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 venlafaxine should be discontinued.

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 administering the drug to patients with tachyarrhythmia.

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.

When receiving venlafaxine, especially in conditions of dehydration or a decrease in blood volume (including in elderly patients and patients taking diuretics), hyponatremia and / or the syndrome of inadequate secretion of antidiuretic hormone (SIADH).

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 3 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. These symptoms are usually observed in the first days after drug withdrawal, although there have been 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").

Women of childbearing age should apply appropriate methods of contraception during the administration of venlafaxine.

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

In healthy volunteers, the drug has virtually no effect on the rate of psychomotor reactions, cognitive abilities and complex behavioral responses. However, given the possibility of significant side effects from the central nervous system, care should be taken during the treatment period when driving vehicles and engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Tablets of prolonged action, film-coated, 37.5 mg, 75 mg and 150 mg.

Packaging:

Tablets 37.5 mg: 7, 10 or 14 tablets per blister Aluminum foil / Aluminum foil. 1, 2, 4, 7, 8 blisters of 7 tablets, 1, 2, 3, 4, 5, 10 blisters with 10 tablets, or 1, 2, 4, 7 of blisters on 14 tablets together with instructions for use in cardboard tutu.

Tablets 75 mg: 5 or 7 tablets per blister Aluminum foil / Aluminum foil. For 2, 4, 6, 8, 10 blisters for 5 tablets or 1, 2, 4, 7, 8 blisters for 7 tablets together with instructions for use in a cardboard box.

150 mg tablets: 5 or 6 tablets per blister Aluminum foil / Aluminum foil. For 2, 4, 6, 10 blisters for 5 tablets or 5, 10 blisters for 6 tablets together with instructions for use in a pack of cardboard.

For all dosages: 10, 30, 60, 100 blisters together with instructions for use in a cardboard box (for hospitals).

When packaged / packaged at a Russian enterprise ZAO-Zdorovye ZAO:

Tablets 37.5 mg: for 7, 10 or 14 tablets in a contour non-cellular package made of aluminum foil. 1, 2, 4, 7, 8 contour non-jawed packages of 7 tablets, 1, 2, 3, 4, 5, 10 contour non-jawed packages of 10 tablets or 1, 2, 4, 7 contour non-jawed packages of 14 tablets together with instructions for use put in a pack of cardboard.

Tablets 75 mg: on 5 or 7 tablets in a contour non-cellular package made of aluminum foil. For 2, 4, 6, 8, 10 contour non-jawed packages of 5 tablets or 1, 2, 4, 7, 8 contour non-jammed packages of 7 tablets together with the instruction for use are placed in a pack of cardboard.

For all dosages: 10, 30, 60, 100 contour non-jawed packages together with instructions for use are placed in a box of corrugated cardboard (for hospitals).

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003781/09

Date of registration:18.05.2009

The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland

Manufacturer: & nbsp

ZIO-HEALTH, JSC Russia

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp14.12.2015

Illustrated instructions

Instructions

Epevelone retard (Efevelon retard)