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

Excipients: lactose monohydrate 18.33 mg, microcrystalline cellulose 45.89 mg, croscarmellose sodium 3 mg, povidone K30 4 mg, magnesium stearate 0.5 mg;

film coating: opadrai 03V23319 orange (hypromellose 1.875 mg, titanium dioxide 0.908 mg, macrogol / PEG 400 0.188 mg, dye yellow color FCF 0.03 mg).

1 tablet, coated, 37.5 mg contains:

active substance: venlafaxine hydrochloride 42.42 mg (corresponding to 37.5 mg venlafaxine);

Excipients: lactose monohydrate 27.5 mg, microcrystalline cellulose 68.83 mg, croscarmellose sodium 4.5 mg, povidone K30 6 mg, magnesium stearate 0.75 mg;

film coating: opadrai 03V23319 orange (hypromellose 2,813 mg, titanium dioxide 1,362 mg, macrogol / PEG 400 0.282 mg, dye yellow color FCF 0.045 mg).

1 tablet, coated, 50 mg contains:

active substance: venlafaxine hydrochloride 56.56 mg (in terms of venlafaxine 50 mg);

Excipients: lactose monohydrate 36.67 mg, microcrystalline cellulose 91.77 mg, croscarmellose sodium 6 mg, povidone K30 8 mg, magnesium stearate 1 mg;

film coating: opadrai 03V23319 orange (hypromellose 3.75 mg, titanium dioxide 1.815 mg, macrogol / PEG 400 0.375 mg, dye yellow color FCF 0.06 mg).

1 tablet, coated, 75 mg contains:

active substance: venlafaxine hydrochloride 84.84 mg (in terms of venlafaxine 75 mg);

Excipients: lactose monohydrate 55 mg, cellulose microcrystalline 137.66 mg, sodium croscarmellose 9 mg, povidone K30 12 mg, magnesium stearate 1.5 mg;

film coating: opadrai 03V23319 orange (hypromellose 5,625 mg, titanium dioxide 2,725 mg, macrogol / PEG 400 0.563 mg, dye yellow color FCF 0.09 mg).

Description:

Round, biconvex tablets, coated, orange, labeled on one side - "V1" for tablets 25 mg, "V2" for tablets 37.5 mg, "V 3" for tablets of 50 mg; tablets with a dosage of 75 mg with risks from both sides, side risks and labeling "V" on the one hand risks and "4" on the other hand risks.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Venlafaxine, an antidepressant not chemically related to any class of antidepressants (tricyclic, tetracyclic or other), is a mixture of two active enantomers.

The mechanism of antidepressant drug effect is associated with its ability to potentiate the transmission of the nerve impulse in the central nervous system (CNS). Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA), are potent inhibitors of the reuptake of serotonin and norepinephrine (SNRI) and weak inhibitors of dopamine reuptake. Besides, venlafaxine and EFA reduce beta-adrenergic reactivity both after a single administration and at a constant intake. Venlafaxine and EFA are equally effective in reversing the capture of neurotransmitters.

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:

Venlafaxine is well absorbed from the gastrointestinal tract. After a single admission of 25-150 mg, the maximum concentration in the blood plasma reaches 33-172 ng / ml for about 2.4 hours. Exposed to intensive metabolism at the first passing through the liver. Its main metabolite is O-desmethylvenlafaxine (EFA). The half-life of venlafaxine and EFA is 5 and 11 hours, respectively. The maximum concentration of EFA in blood plasma is 61-325 ng / ml achieved approximately 4.3 hours after administration.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 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:

Treatment of depression and prevention of relapse.

Contraindications:

- Hypersensitivity;

- aboutsimultaneous administration of MAO inhibitors (see section "Interaction");

- severe impairment of kidney and / or liver function (glomerular filtration rate (GFR) 10 ml / min);

- age to 18 years (safety and efficacy for this age group are not proven);

- established pregnancy or suspected pregnancy;

lactation period.

Carefully:

Recently suffered myocardial infarction, unstable angina, arterial hypertension, tachycardia, a history of convulsive syndrome, increased intraocular pressure, closed-angle glaucoma, manic conditions in the anamnesis, a predisposition to bleeding from the skin and mucous membranes, initially reduced body weight.

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:

The drug is taken orally, preferably at the same time, during meals, the tablets are not chewed and washed down with liquid.

The recommended initial dose is 75 mg in two divided doses (37.5 mg daily). The recommended dosage for depression of moderate severity is 225 mg / day in 3 divided doses. If necessary, the dosage can be increased at intervals of not less than 4 days by 75 mg / day.

If after several weeks of treatment there is no significant improvement, the daily dose can be increased to 150 mg (2 x 75 mg per day). If, in the doctor's opinion, a higher dose is required (severe depressive disorder or other conditions requiring hospital treatment), 150 mg can be given immediately in two divided doses (2 x 75 mg per day).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 the drug Epevelon is 375 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:

Supportive treatment can last 6 months or more. The minimum effective doses used in the treatment of a depressive episode are prescribed.

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 25-50%. In connection with the elongation 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 may receive 50% of the usual daily dose of venlafaxine after the completion of hemodialysis.

Liver failure: with mild hepatic insufficiency (prothrombin time (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 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.

Discontinuation of the drug

At the end of taking Epevelone, it is recommended to gradually reduce the dosage of the drug, at least within a week, and monitor the patient's condition in order to minimize the risk associated with withdrawal of the drug (see below).

The period required to completely stop taking the drug depends on its dosage, the length of the course of treatment and the individual characteristics of the patient.

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%, infrequent> 0.1% - <1%, rare> 0.01% - <0.1%, very rare <0.01%.

General symptoms: weakness, increased fatigue.

Co hand gastrointestinal tract: loss of appetite, constipation, nausea, vomiting, dry mouth; rarely: hepatitis.

From the side of metabolism: increased serum cholesterol levels, weight loss; infrequent: changes in laboratory tests of liver function, hyponatremia, syndrome of insufficient secretion of antidiuretic hormone.

From the side of the cardiovascular system: arterial hypertension, hyperemia of the skin; infrequent: postural hypotension, tachycardia.

From the nervous system: unusual dreams, dizziness, insomnia, increased excitability, paresthesia, stupor, increased muscle tone, tremor; infrequent: apathy, hallucinations, muscle spasms, serotonin syndrome; rare: epileptic seizures, manic reactions, as well as symptoms resembling malignant neuroleptic syndrome (CNS).

Co hand urogenital system: violations of ejaculation, erections, anorgasmia, dysuric disorders (mainly - difficulties in the beginning of urination); infrequent: decreased libido, menorrhagia, urinary retention.

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

Co hand skin integument: sweating; infrequent: reactions of photosensitivity; rare: erythema multiforme, Stevens-Johnson syndrome.

Co hand hematopoiesis systems: infrequent: hemorrhages in the skin (ecchymoses) and mucous membranes, thrombocytopenia; rare: prolonged bleeding time.

Hypersensitivity reactions: infrequent: skin rash; very rare: anaphylactic reactions.

After severe cancellation of venlafaxine or a decrease in its dose, fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, increased irritability, disorientation, hypomania, paresthesia, sweating may be observed. 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.

Overdose:

Symptoms: ECG changes (lengthening of the interval QT, bundle branch blockade, expansion of the complex QRS), sinus or ventricular tachycardia, bradycardia, hypotension, convulsive states, alteration, consciousness (decreased wakefulness level).

In case of an overdose of venlafaxine with concomitant intake with alcohol and / or other psychotropic drugs, a fatal outcome was reported.

Treatment: symptomatic. Specific antidotes are unknown. Recommendedcontinuous 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 is contraindicated. The drug Ephevelon can be started 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 Epevelon.

Venlafaxine does not affect the pharmacokinetics lithium.

When used simultaneously with imipramine the pharmacokinetics of venlafaxine and its metabolite O-desmethylvenlafaxine (EFA) does not change.

Haloperidol: the effect of the latter can be enhanced by the increase in the level of the drug in the blood in a joint application.

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 the development of side effects (eg, epileptic seizures).

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

Strengthens the influence alcohol on psychomotor reactions.

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 P 450 isoenzymes

Enzyme CYP2D6 of the cytochrome P 450 system 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 active substance and metabolite (venlafaxine and EFA) will not change.

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 O-desmethylvenlafaxine.In most patients, only a slight increase in the total pharmacological activity of venlafaxine and O-desmethylvenlafaxine is expected (more pronounced in elderly patients and in liver failure).

Clinically significant interactions of venlafaxine with antihypertensive (including beta-blockers, ACE inhibitors and diuretics) and antidiabetic drugs not detected.

Drugs associated with blood plasma proteins: protein binding plasma is 27% for venlafaxine and 30% for EFA. therefore 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.

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

Special instructions:

Abolition of the drug Epevelon

As with the treatment with other antidepressants, a sharp discontinuation of venlafaxine therapy - especially after high doses of the drug - can cause withdrawal symptoms, which is why it is recommended that the dose be gradually lowered before the drug is withdrawn. The length of the period necessary to reduce the dose depends on the size of the dose, the duration of therapy, as well as the individual sensitivity of the patient.

When prescribing Epevelone, patients with lactose intolerance should take into account the content of lactose (56.62 mg in each tablet 25 mg, 84.93 mg in each tablet 37.5 mg, 113.24 mg in each tablet 50 mg, 169.86 mg in each tablet 75 mg).

In patients with depressive disorders, the likelihood of suicidal attempts should be considered before initiating any drug therapy. Therefore, in order to reduce the risk of overdose, the initial dose of the drug should be as low as possible, and the patient should be under careful medical supervision.

In patients with affective disorders in the treatment of antidepressants, including venlafaxine, hypomanic or manic conditions may occur.

Like other antidepressants, venlafaxine must be administered with caution to a patient 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.

Patients should be warned about the need to consult a doctor immediately if rashes, urticaria 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 during the period of clarification or increase in dosage.

An increase in heart rate may occur, especially during high doses. Care is advised with tachyarrhythmias.

Patients, especially the elderly, should be warned about the possibility of dizziness and discomfort.

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 the drug may be observed mydriasis, in connection with which it is recommended to control intraocular pressure in patients prone to its increase or suffering from an angle-closure glaucoma.

There is insufficient data on the use of venlafaxine in patients who have recently undergone myocardial infarction and who suffer from decompensated heart failure. Such patients should be administered with caution.

The clinical trials conducted to date have not revealed a tolerance to, or dependence on, venlafaxine. Despite this, as with other drugs acting on the central nervous system, the physician must establish close monitoring of patients to identify signs of drug abuse. Careful monitoring and follow-up are necessary for patients who have a history of such symptoms.

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

Although venlafaxine does not affect psychomotor and cognitive functions, 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.

Also, alcohol is not recommended.

Form release / dosage:The coated tablets are 25 mg, 37.5 mg, 50 mg and 75 mg.

Packaging:

10 tablets per blister.

For 3 or 6 blisters together with instructions for use in the pack.

For 10, 30, 60, 100 blisters, along with instructions for use in a cardboard box (for hospitals).

Storage conditions:In a dry place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001391

Date of registration:17.06.2011

The owner of the registration certificate:AKTAVIS, LTD. AKTAVIS, LTD. Russia

Manufacturer: & nbsp

AKTAVIS, LTD. Russia

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp13.12.2015

Illustrated instructions

Instructions

Ephevelone (Efevelon)