Venlaxor - instructions for use, doses, side effects, contraindications

Excipients: calcium hydrophosphate anhydrous, lactose anhydrous, carboxymethyl starch sodium, magnesium stearate, silicon dioxide colloidal anhydrous, iron oxide red (E 172).

Description:

Tablets of 37.5 mg: light pink planocylindrical tablets with dark pink patches, with a facet and a risk on one side.

Tablets of 75 mg: light pink planocylindrical tablets with dark pink patches, with a facet and a risk on one side.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Venlafaxine - an antidepressant that does not chemically belong to any class of antidepressants (tricyclic, tetracyclic or other), is a racemate 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 serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Besides, venlafaxine and O-desmethylvenlafaxine 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-aspartane (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. It is subject to intensive metabolism at the first passage 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 during meals, 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, the concentrations in the blood plasma of venlafaxine and EFA are increased, and their elimination rate 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 of various etiologies, treatment and prevention.

Contraindications:

Hypersensitivity.

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

Severe renal and / or hepatic impairment (glomerular filtration rate less (GFR) 10 ml / min).

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

Prescribed or suspected pregnancy.

Lactation period.

Carefully:

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

Pregnancy and lactation:

The safety of venlafaxine during pregnancy is not proven, so the use of the drug during pregnancy (or presumptive pregnancy) is contraindicated. 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.

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

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.

Dosing and Administration:

Venloxor ® tablets should be taken with food.

The recommended initial dose is 75 mg in two divided doses (37.5 mg daily).

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 Venlaxor ® 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 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 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 appointment of other medications, caution is required in the treatment of elderly patients, for example, due to the possibility of impaired renal function. The lowest effective dose should be used. When the dose is raised, the patient should be under careful medical supervision.

Termination of Venlaxor®:

At the end of taking VENLAKSOR®, it is recommended to gradually reduce the dosage of the drug for at least 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.

Depending on the frequency of occurrence, the following groups of side effects are distinguished: frequent - more than 1%, infrequent - 0,1-1%, rare - 0,01-0,1%, very rare - less than 0,01%.

From the nervous system: often - dizziness, asthenia, insomnia, "nightmarish" dreams, increased nervous excitability, paresthesia, hypertonic muscle, tremor, sedation; infrequently - apathy, hallucinations, myoclonus, syncope; rarely - convulsions, manic disorders, malignant neuroleptic syndrome.

From the side of the cardiovascular system: often - increased blood pressure, hyperemia of the skin; infrequently - lowering blood pressure, postural hypotension, tachycardia; very rarely - a change in the Q-T interval, ventricular fibrillation, ventricular tachycardia (including ventricular fibrillation).

From the digestive system: often - decreased appetite, nausea, vomiting; infrequently - bruxism (involuntary grinding of teeth), increased activity of "liver" transaminases; rarely - hepatitis.

From the genitourinary system: often - decreased libido, erectile dysfunction and / or ejaculation, anorgasmia, menorrhagia, urination disorder; infrequently - urinary retention, violation of orgasm in women.

From the sense organs: often - a violation of accommodation, mydriasis, impaired vision; infrequent - a violation of taste perception.

From the hematopoiesis: frequency unknown - agranulocytosis, aplastic anemia, neutropenia, pancytopenia.

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

Laboratory indicators: infrequently - thrombocytopenia; rarely - increased bleeding time, hyponatremia; with long-term administration and use of high doses - hypercholesterolemia.

Other: often - loss of body weight, sweating (including night); infrequently - ecchymosis, weight gain; rarely - Syndrome of inappropriate secretion of antidiuretic hormone, serotonin syndrome (nausea, vomiting, abdominal pain, diarrhea, flatulence, agitation, tachycardia, hyperthermia, muscle stiffness, convulsion, myoclonus, sweating, inhibition of consciousness of varying severity).

PIn the event of the syndrome of "cancellation": dizziness, headache, asthenia, fatigue, sleep disturbances (change in the nature of dreams, drowsiness or insomnia, difficulty falling asleep), hypomania, anxiety, irritability, confusion, paraesthesia,increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are slightly expressed and do not require treatment).

Overdose:

Symptoms: ECG changes (lengthening interval QT, bundle branch blockade, expansion of the complex QRS), sinus or ventricular tachycardia, bradycardia, hypotension, convulsive states, alteration of consciousness (decrease in wakefulness level). In case of an overdose of venlafaxine with simultaneous reception with alcohol and / or other psychotropic drugs, a fatal 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 is contraindicated. The preparation of Venlaxor® can be started no less than 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 cancellation of VENLAKSOR®.

Venlafaxine does not affect the pharmacokinetics lithium.

When used simultaneously with imipramine the pharmacokinetics of venlafaxine and its metabolite 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 AUC risperidone) the pharmacokinetics of the sum of 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 under these conditions.

Drugs metabolized cytochrome P 450:

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 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).

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

Drugs associated with blood plasma proteins: binding to plasma proteins is 27% for venlafaxine and 30% for EFA. Therefore, does not affect the concentration of drugs in 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 of C_mOh), and the pharmacokinetics of venlafaxine and EFA do not change. However, the clinical significance of this effect is unknown.

Special instructions:

Cancellation of the drug Venlaksor®: 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 to gradually lower the dose before stopping the drug. 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.

When appointing Venlaxor® tablets, patients with lactose intolerance should take into account the lactose content (30 mg in each tablet 37.5 mg, 60 mg in each 75 mg tablet).

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 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 during the period of selection or increase of the dose.

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.

When taking 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 hormone can 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 suffering from an angle-closure glaucoma.

Venlafaxine has not been studied in patients who have recently had myocardial infarction and who suffer from decompensated heart failure. Such patients should be administered with caution.

Patients should be monitored to identify signs of drug abuse, especially for patients who have a history of such symptoms.

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: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:Tablets, 37.5 mg and 75 mg.

Packaging:

Tablets of 37.5 mg: 10 tablets in a blister made of polyvinyl chloride film and aluminum foil. For 3 blisters along with the instruction is placed in a pack of cardboard.

Tablets of 75 mg: 10 tablets in a blister made of polyvinyl chloride film and aluminum foil. For 3 blisters along with the instruction is placed in a pack of cardboard.

Storage conditions:In the dark place 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002525/07

Date of registration:31.08.2007

Expiration Date:Unlimited

The owner of the registration certificate:GRINDEX, JSC GRINDEX, JSC Latvia

Manufacturer: & nbsp

GRINDEX, AO Latvia

Representation: & nbspGrindeks Rus, Open CompanyGrindeks Rus, Open CompanyRussia

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Venlaxor® (Venlaxor®)