Venlift OD - instructions for use, dose, side effects, contraindications

Capsule shell composition: gelatin 82.46%, water 14.5%, sodium lauryl sulfate 0.08%, methyl parahydroxybenzoate 0.8%, propyl parahydroxybenzoate 0.2%, dye crimson [Ponso 4R] 0.003%; titanium dioxide 1.95%; dye sunset yellow 0.0105%.

Dosage of 75 mg:

active substance: venlafaxine hydrochloride 84.85 mg in terms of venlafaxine 75 mg (in the form of pellets);

pellet auxiliaries: sugar grits [sucrose, molasses starch] 50.26 mg; hypromellose 2910 E15 LV 6.72 mg, silicon colloidal dioxide 6.72 mg;

Excipients: ethylcellulose 45 cps 14.28 mg; hypromellose 6 cPs 1.98 mg;

fromleft capsule shell: gelatin 83.13%, water 14.5%, sodium lauryl sulfate 0.08%, methyl parahydroxybenzoate 0.8%, propyl parahydroxybenzoate 0.2%, titanium dioxide 0.975%, dye sunset yellow 0.0165%; dye quinoline yellow 0.3%.

Dosage of 150 mg:

active substance: venlafaxine hydrochloride 169.70 mg in terms of venlafaxine 150 mg (in the form of pellets);

pellet auxiliaries: sugar grits [sucrose, molasses starch] 100.52 mg, hypromellose 2910 E15 LV 13.44 mg, silicon colloidal dioxide 13.44 mg;

Excipients: ethylcellulose 45 cps 28.56 mg; hypromellose 6 cps 3.96 mg;

composition of the capsule shell: gelatin 81.72%, water 14.5%, sodium lauryl sulfate 0.08%, methyl parahydroxybenzoate 0.8%, propyl parahydroxybenzoate 0.2%, dye crimson [Ponso 4R] 0.06%; titanium dioxide 2.4375%; dye sunset sunset yellow .098%.

Description:

37.5 mg: Hard gelatin capsules (№ 4) with a lid from light pink to yellow-pink color and a transparent body from light pink to yellow-pink color, containing pellets of white or almost white color.

75 mg: Hard gelatin capsules (No. 2) with a yellow lid and a transparent yellow body, containing pellets of white or almost white color.

150 mg: Hard gelatin capsules (No. 0) with an orange lid and a transparent orange casing, containing white or almost white pellets.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Venlafaxine and its main metabolite O-desmethylvenlafaxine (EFA) are potent inhibitors of reuptake of serotonin and norepinephrine and weak inhibitors of dopamine reuptake.The mechanism of action is associated with increased activity of neurotransmitters in the central nervous system (CNS). Venlafaxine and EFA in vitro have no significant affinity for muscarinic, histaminergic, alpha 1 -adrenergic receptors, do not have the ability to inhibit monoamine oxidase (MAO) activity. On the inhibition of serotonin reuptake venlafaxine is inferior to selective serotonin reuptake inhibitors.

Pharmacokinetics:

Suction and distribution

Absorption - 92%, does not depend on food intake, absorption of prolonged-action capsules is slower than tablets; bioavailability - 40-45%, which is associated with presystemic metabolism. Time to reach the maximum concentration in the blood plasma (TC_mOh) venlafaxine and EFA - 5.5 and 9 h respectively. The equilibrium concentration (Css) venlafaxine and its active metabolite (EFA) in plasma are achieved within 3 days of admission. The connection with plasma proteins venlafaxine and EFA - 27% and 30%, respectively. Venlafaxine and EFA permeate into breast milk.

Metabolism

Metabolized mainly with the formation of a single pharmacologically active metabolite (EFA), as well as several inactive- N-desmethylvenlafaxine, N, O-didezmethylvenlafaxine and others. In patients with reduced isoenzyme activity CYP2D6 there is 2-3 times greater venlafaxine exposure and 2-3 times less exposure to the active metabolite of EFA.

Excretion

It is mainly excreted by the kidneys: approximately 87% of the dose is excreted in the urine for 48 hours (5% unchanged, 29% unconjugated EFA, 26% conjugated EFA, 27% other inactive metabolites).

Pharmacokinetics in special clinical cases

Pharmacokinetics in selected patient groups

Elderly patients

Pharmacokinetic parameters do not depend on sex and age.

Patients with impaired renal or hepatic function

In patients with impaired liver function (with cirrhosis in the stage of compensation), there was a decrease in the metabolism of venlafaxine and the excretion of its active metabolite, which led to an increase in their concentration in the blood plasma.

In patients with mild or severe renal dysfunction, there was a decrease in venlafaxine metabolism and elimination of EFA, which led to an increase in their maximum concentration in blood plasma (C_mOh), decrease in clearance and elongation of the half-life (T_1/2). The decrease in overall clearance was most pronounced in patients with creatinine clearance (CC) below 30 ml / min.

Indications:

Depression.

Contraindications:

Hypersensitivity to venlafaxine or any component of the drug, simultaneous administration of MAO inhibitors, children and adolescents under the age of 18, sugar / isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption.

Carefully:

Recent myocardial infarction, unstable angina, hypertension, tachycardia, cramps in history, ocular hypertension, angle-closure glaucoma, manic state history, hyponatremia, hypovolemia, dehydration, simultaneous diuretics, suicidal predisposition to bleeding from the skin and mucous membranes shells, renal / hepatic insufficiency.

Pregnancy and lactation:

In pregnancy, use is possible if the expected benefit for the mother exceeds the potential risk to the fetus (adequate and strictly controlled safety studies in pregnant women are not performed).

If venlafaxine apply before or immediately before childbirth, it is necessary to take into account the possibility of developing the "cancellation" reactions in a newborn.

The effect of venlafaxine on labor and delivery in humans is unknown.

Venlafaxine and its active metabolite EFA penetrate the breast milk of women. Given the potential risk of serious side effects in breast-fed infants, lactating women should discontinue either breastfeeding or the use of the drug (in accordance with the importance of the drug for the mother).

Dosing and Administration:

Venlift OD is taken orally during meals preferably at the same time, in the morning or in the evening. Capsules must be swallowed whole, squeezed with liquid.

The recommended initial dose is 75 mg once a day; if necessary, increase the dose at intervals of at least 4 days to 2 weeks or more. The maximum daily dose is 225 mg. Patients receiving tablets can be switched to receive capsules in similar doses.

Cancellation of the drug should be carried out gradually to avoid the syndrome of "withdrawal": in the course of treatment for 6 weeks or more, the period of gradual withdrawal of the drug should be at least 2 weeks and depends on the dose,duration of therapy and individual characteristics of the patient (in the course of clinical studies of the capsules, the dose was reduced by 75 mg once a week).

In case of impaired renal function (the rate of glomerular filtration is 10-70 ml / min), the daily dose should be reduced by 25-50%.

In hemodialysis, the daily dose should be reduced by 50%, the drug should be taken after the end of the hemodialysis session.

In patients with hepatic insufficiency the average daily dose should be reduced by 50% or more.

Side effects:

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 central nervous and peripheral system: often - dizziness, asthenia, weakness, insomnia, "nightmarish" dreams, increased nervous excitability, paresthesia, hypertonic muscle, tremor, sedation, anorexia; infrequently - apathy, hallucinations, myoclonus, violations of orgasm in women, convulsive disorders; rarely - convulsions, manic condition, malignant neuroleptic syndrome; rarely - manic disorders, serotonin syndrome,akathisia, mania or hypomania; very rarely - delirium, psychomotor agitation, extrapyramidal reactions (dystonia and dyskinesia), tardive dyskinesia.

From the side of the cardiovascular system: often - increased blood pressure, vasodilation (very often a sense of "hot flush"), flushing of the skin; infrequently - decreased blood pressure, postural hypotension, arrhythmias (including tachycardia), fainting; rarely - hemorrhage (including cerebral hemorrhage); very rarely (when taking capsules) - changing the interval Q-T, 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, gastrointestinal bleeding.

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, noise in the ears; very rarely - angle-closure glaucoma.

On the part of the organs of hematopoiesis: infrequently - hemorrhages in the skin (ecchymosis), bleeding of the mucous membranes; rarely - increased bleeding time, thrombocytopenia; very rarely - blood dyscrasia (agranulocytosis, aplastic anemia, neutropenia, pancytopenia).

From the immune system: very rarely - anaphylactic reactions, hyperprolactinemia.

Allergic reactions: infrequent - rash, photosensitivity; very rarely - multiforme exudative erythema (including Stevens-Johnson syndrome), urticaria, 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, hyperperespiration (including nocturnal), yawning; infrequently - ecchymosis, weight gain; rarely syndrome of inadequate secretion of ADH, serotonin syndrome (nausea, vomiting, abdominal pain, diarrhea, flatulence, psychomotor agitation, tachycardia, hyperthermia, muscle rigidity, convulsions, myoclonus, sweating (including night sweating), impaired consciousness from delirium to sopor and coma with a subsequent fatal outcome).

From the side of metabolism: often - increased serum cholesterol levels (especially with long-term treatment and, possibly, high doses), weight loss; infrequently - hyponatremia, weight gain; rarely - the syndrome of inappropriate production of antidiuretic hormone (ADH); very rarely - an increase in the level of prolactin in the blood.

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

Messages Received in the postmarketing period (causal relationship with venlafaxine is not established) include the following adverse reactions: angioedema, catatonia, malformations, impaired coordination and sense of balance, increased activity of creatine phosphokinase, deep vein thrombosis, toxic epidermal necrolysis.closed-angle glaucoma, bleeding from the mucous membranes of the eyes, side reactions from the liver (including increased activity of gamma-glutamyltransferase, changes in functional liver samples, liver damage (necrolysis or liver failure, fatty liver infection), interstitial lung disease, involuntary movements, increased lactate dehydrogenase activity, pancreatitis, panic reaction, renal failure, rhabdomyolysis, impaired sensitivity (including sensation of electric shock ), And the development of hyponatremia syndrome of inappropriate secretion of antidiuretic hormone, especially in elderly patients.

Overdose:

Symptoms (often occurs with simultaneous intake of ethanol): dizziness, lowering blood pressure, changes in ECG (lengthening interval Q-T, bundle branch blockade, expansion of the complex QRS), sinus and ventricular tachycardia, bradycardia, depression of consciousness (from drowsiness to coma), epileptic seizures, rhabdomyolysis, mydriasis, convulsions and death.

Treatment: ensure airway patency, oxygenation and ventilation of the lungs, symptomatic therapy.It is recommended to monitor the ECG and the functions of vital organs; at risk of aspiration, vomiting is not recommended; Washing (if an overdose has occurred recently, or the symptoms of an overdose persist); Activated carbon. The effectiveness of forced diuresis, dialysis, hemoperfusion and blood transfusion has not been proven; specific antidotes are unknown.

Interaction:

Incompatible with MAO inhibitors.

Reduces AUC indinavir by 28% and its C_mOh - by 36% (the clinical significance of the established phenomenon is unknown).

Increases the anticoagulant effect of warfarin.

Increases the effect of ethanol on psychomotor reactions.

When oral intake reduces the total clearance of haloperidol by 42%, increases it AUC by 70% and C_mOh by 88%.

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).

Has no effect on the pharmacokinetics of imipramine and 2-hydroxyimipramine, but the indices AUC, FROM_mOh and the minimum concentration (C_min) of desipramine increase by 35%, a AUC 2-hydroxyimipramine in 2.5-4.5 times.

Raises the AUC risperidone by 32%, but does not significantly affect the total pharmacokinetic profile of the active components - risperidone plus 9-hydroxyrisperidone (the clinical significance of the phenomenon is unknown).

Does not interact with lithium preparations, as well as drugs metabolized by enzymes CYP3A4, CYP1A2 and CYP2C9 (including alprazolam, caffeine, carbamazepine, diazepam).

Does not affect the concentration of drugs in the plasma, which have a high degree of binding to proteins.

Drugs metabolized by cytochrome P 450 isoenzymes

Enzyme CYP2C6 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 CYP2C6, or in patients with a genetically determined decrease in activity CYP2C6, since the total concentration of active substance and metabolite (venlafaxine and EFA) will not change.

The main way of removing venlafaxine involves metabolism involving CYP2C6 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 CYP2C6 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.

Special instructions:

Clinical impairment and risk of suicide

In children, adolescents and young adults (under 24 years) with depression and other mental disorders antidepressants compared to placebo, increased the risk of suicidal thoughts or suicidal behavior. Therefore, when appointing venlafaxine or any other antidepressant drugs in children, adolescents and young people (younger than 24 years), the risk of suicide and the benefits of their use should be correlated. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide.Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies.

Before initiating treatment with antidepressants, patients with signs of depression should undergo a screening to determine the risk of bipolar disorder, beginning with a thorough examination of personal and family history.

The combination with MAO inhibitors (see "Contraindications")

Taking venlafaxine is possible no earlier than 14 days after discontinuation of therapy with MAO inhibitors and in turn should be discontinued no less than 7 days before any MAO inhibitor starts. With the simultaneous administration of venlafaxine and MAO inhibitors, it is possible to develop severe adverse reactions (including tremor, myoclonus, excessive sweating, nausea, vomiting, flush, developing and increasing dizziness, hyperthermia with signs similar to neuroleptic malignant syndrome; the autonomic nervous system with possible rapid fluctuations in the basic indices of vital activity, changes in the mental state,including the extreme degree of development of agitation, progressing to delirium and coma; cramps, up to a lethal outcome).

Activation of mania / hypomania

In patients with effective disorders in the treatment of antidepressants, including venlafaxine, hypomanic or manic conditions may occur. Like other antidepressants, venlafaxine should be administered with caution to patients with a history of mania. Such patients need medical supervision.

Convulsions

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.

Hemorrhages

Like other serotonin reuptake inhibitors, venlafaxine can increase the risk of hemorrhages in the skin and bleeding from the mucous membranes, so care must be taken when used in patients with a predisposition to such conditions.

Mydriasis

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.

Hyponatremia

On the background of treatment in patients with hypovolemia or in dehydrated patients (including elderly patients and taking diuretics), hyponatremia and / or the syndrome of inadequate secretion of antidiuretic hormone may develop.

The "cancellation" syndrome

As with the treatment with other antidepressants, a sharp discontinuation of venlafaxine can cause withdrawal syndrome. The risk of developing the withdrawal syndrome depends on the duration of the course of treatment, the dose used, and the rate at which it is reduced. With the withdrawal syndrome, dizziness, paresthesia, sleep disturbance, agitation, anxiety, nausea, vomiting, tremor, sweating, headache, diarrhea, tachycardia, emotional disorders appear. These symptoms are usually noted in the first days after the drug is withdrawn and pass independently for 2 weeks. Therefore, the drug should be withdrawn gradually, reducing the dose of venlafaxine gradually over several weeks or months, depending on the patient's condition.

Changes in appetite and body weight

Based on the results of short-term, double-blind, placebo-controlled studies in patients with depression, the most common reported occurrence of venlafaxine anorexia (8%) compared withplacebo (4%). Dose-dependent weight loss was often noted in patients taking venlafaxine in a few weeks. Significant weight loss, especially in patients with depression that are too light, may be an undesirable effect of venlafaxine treatment. The cessation of progression of anorexia and weight loss in patients with depression with venlafaxine was rarely observed-1 and 0.1%, respectively.

In short-term (up to 8 weeks) studies in patients with generalized anxiety disorder who received venlafaxine, anorexia was noted in 8% of cases (placebo - 2%). A decrease in body weight of 7% or more was observed in 3% of patients who received venlafaxine for a period up to 6 months (placebo - 1%). The cessation of progression of anorexia and weight loss for a period of up to 8 weeks was observed in 0.9% and 0.3% of patients, respectively.

In studies in patients with social phobias for up to 12 weeks, anorexia was noted in 20% of cases (placebo - 2%). Decrease in body weight by 7% or more was not observed in patients who received venlafaxine for a period of up to 12 months, or in the placebo group.The cessation of progression of anorexia and a decrease in body weight over a period of up to 12 weeks was 0.4% and 0.0%, respectively.

Nervousness and insomnia

A combined analysis of short-term studies in patients with depression, generalized anxiety disorder and social phobias showed that the most common effects associated with taking venlafaxine compared with placebo were insomnia and nervousness (in brackets, percentage in the placebo group). Insomnia was noted in 17% of cases (11%), nervousness - 10% (5%) in patients with a depressive episode (n= 357) compared with placebo (n= 285); 15% (10%) and 6% (4%) in patients with generalized anxiety disorder (n= 1381) compared with placebo (n= 555); 23% (7%) and 11% (3%) in patients with social phobias (n= 277) compared with placebo (n= 274), respectively.

In the treatment of patients with a depressive episode, 0.9% of patients discontinued treatment due to insomnia and 0.9% because of the appearance of nervousness. In patients with generalized anxiety disorder, during treatment for up to 8 weeks, insomnia and nervousness caused the discontinuation of therapy in 3 and 2% of cases, with treatment duration of up to 6 months in 2 and 0.7% of cases, respectively.In patients with social phobias, up to 12 weeks of treatment, insomnia caused the cancellation of venlafaxine in 3% of cases, nervousness was not the reason for discontinuing the drug.

Some patients received a dose-dependent increase in arterial pressure during venlafaxine intake, and regular blood pressure monitoring is recommended, especially during the period of correction or increase in the dose.

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

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

During treatment it is recommended to refrain from taking ethanol.

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

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Capsules of prolonged action, 37.5 mg, 75 mg and 150 mg.

Packaging:

For 7 or 10 capsules in an aluminum foil blister.

For 1, 2, 3, 4, 5, 6 or 10 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store at a temperature not exceeding 30 ° 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:LP-001221

Date of registration:16.11.2011 / 11.09.2012

Expiration Date:16.11.2016

Date of cancellation:2017-08-16

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp16.08.2017

Illustrated instructions

Instructions

VENLIFT OD (Venlift OD)