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Effexor XR

Effexor XR
Effexor Xr is mainly used to treat depression, general anxiety disorder, social phobia, panic disorder and vasomotor symptoms.

Brand: Venlafaxine

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: September 2023
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Effexor XR 150 mg
360 pills - 150 mg
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$325.26 $0.90 $322.38 Add to cart
270 pills - 150 mg
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$247.97 $0.92 $237.76 Add to cart
180 pills - 150 mg
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$182.99 $1.02 $140.83 Add to cart
120 pills - 150 mg
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$135.98 $1.13 $79.90 Add to cart
90 pills - 150 mg
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$108.95 $1.21 $52.96 Add to cart
60 pills - 150 mg $81.99 $1.37 $25.95 Add to cart
30 pills - 150 mg $53.97 $1.80 No Add to cart
Effexor XR 75 mg
360 pills - 75 mg
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$287.99 $0.80 $311.89 Add to cart
270 pills - 75 mg
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$222.21 $0.82 $227.70 Add to cart
180 pills - 75 mg
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$158.99 $0.88 $140.95 Add to cart
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$114.99 $0.96 $84.97 Add to cart
90 pills - 75 mg $94.99 $1.06 $54.98 Add to cart
60 pills - 75 mg $70.99 $1.18 $28.99 Add to cart
30 pills - 75 mg $49.99 $1.67 No Add to cart
Effexor XR 37.5 mg
360 pills - 37.5 mg
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$249.99 $0.69 $253.89 Add to cart
270 pills - 37.5 mg
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$191.93 $0.71 $185.98 Add to cart
180 pills - 37.5 mg
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$133.99 $0.74 $117.95 Add to cart
120 pills - 37.5 mg $96.99 $0.81 $70.97 Add to cart
90 pills - 37.5 mg $77.99 $0.87 $47.98 Add to cart
60 pills - 37.5 mg $59.99 $1.00 $23.99 Add to cart
30 pills - 37.5 mg $41.99 $1.40 No Add to cart

Product description

Pharmacodynamics of Effexor XR

Venlafaxine is an antidepressant. According to its chemical structure, it cannot be attributed to any known class of antidepressants (tricyclic, tetracyclic, or others). 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 serotonin and norepinephrine reuptake and weakly suppress dopamine reuptake by neurons. Venlafaxine and EFA are equally effective on neurotransmitter reuptake. Venlafaxine and EFA reduce beta-adrenergic responses.

Venlafaxine has no affinity for muscarinic, cholinergic, histamine H1- and α1-adrenergic receptors in the brain. Venlafaxine does not suppress MAO activity. Has no affinity for opiate, benzodiazepine, phencyclidine or N-methyl-D-aspartate (NMDA) receptors.

Venlafaxine is an antidepressant that does not chemically belong to any class of antidepressants (tricyclic, tetracyclic or others), is a racemate of two active enantiomers.

Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA), are potent SSRIs and weak dopamine reuptake inhibitors.

The mechanism of the antidepressant action of the drug is associated with its ability to potentiate the transmission of nerve impulses to the central nervous system.

Venlafaxine and EFA equally effectively affect the reuptake of the above neurotransmitters, while they have no affinity (studied in vitro) for cholinergic (muscarinic), H1-histamine, alpha1-adrenergic, opiate and benzodiazepine receptors, do not suppress MAO activity. Also do not have an affinity for opiate, phencyclidine or N-methyl-d-aspartate (NMDA) receptors. Venlafaxine is inferior to SSRIs in inhibiting serotonin reuptake. In addition, venlafaxine and EFA reduce beta-adrenergic reactivity both after a single dose and with continuous use.

An antidepressant that does not belong to any known class of antidepressants in its chemical structure (including tricyclic, tetracyclic, or others). It is a racemate of two active enantiomers. The antidepressant effect of venlafaxine is associated with the ability to potentiate the transmission of nerve impulses to the central nervous system. Venlafaxine and its main metabolite O-desmethylvenlafaxine (EFA) are potent inhibitors of the reuptake of serotonin and norepinephrine by neurons and weakly suppress dopamine reuptake. Venlafaxine and EFA reduce the beta-adrenergic reactivity of the central nervous system both after a single dose and with continuous administration.

Venlafaxine has no affinity for m-cholinergic, H1-histamine and α1-adrenergic receptors in the brain. Does not inhibit MAO activity. The drug does not affect the release of norepinephrine from the brain tissue.

Venlafaxine, an antidepressant that does not chemically belong to any class of antidepressants (tricyclic, tetracyclic, or others), is a mixture of two active enantiomers.

The mechanism of the antidepressant effect of the drug is associated with its ability to potentiate the transmission of nerve impulses to the central nervous system. Venlafaxine and its major metabolite O-desmethylvenlafaxine (EFA) are potent serotonin and norepinephrine reuptake inhibitors (SNRIs) and weak dopamine reuptake inhibitors. In addition, venlafaxine and O-desmethylvenlafaxine reduce beta-adrenergic reactivity both after a single dose and when taken continuously. Venlafaxine and EFA are equally effective on neurotransmitter reuptake.

Venlafaxine has no affinity for muscarinic cholinergic, histamine, and α1-adrenergic receptors in the brain. Venlafaxine does not suppress MAO activity. Has no affinity for opiate, benzodiazepine, phencyclidine or N-methyl-d-aspartate (NMDA) receptors.

Pharmacokinetics

After taking Effexor XRa® capsules of prolonged action, Cmax of venlafaxine and EFA (the main metabolite) in plasma are reached within (6.0 ± 1.5) and (8.8 ± 2.2) hours, respectively. The rate of absorption of venlafaxine from sustained-release capsules is lower than the rate of its elimination. Therefore, the T1/2 of venlafaxine after administration of Effexor XRa® in the form of prolonged-release capsules - (15 ± 6) h - is actually the T1/2 of absorption, rather than the T1/2 of distribution - (5 ± 2) h, - which is noted after prescribing Effexor XR® tablets.

Plasma protein binding of venlafaxine and EFA is 27% and 30%, respectively. EFA and other metabolites, as well as unmetabolized venlafaxine, are excreted by the kidneys. With repeated administration ofCss venlafaxineand EFA are achieved within 3 days. Venlafaxine and EFA have linear kinetics in the 75–450 mg daily dose range. After taking the drug during meals, Tmax in blood plasma increases by 20-30 minutes, but the values ​​of Cmax and absorption do not change.

In patients with cirrhosis of the liver, plasma concentrations of venlafaxine and EFA are increased, and the rate of their excretion is reduced. In moderate to severe renal failure, the total clearance of venlafaxine and EFA decreases and T1/2 increases. A decrease in total clearance is mainly observed in patients with Cl creatinine below 30 ml / min.

The age and sex of the patient do not affect the pharmacokinetics of the drug.

Absorption. Absorption from the gastrointestinal tract is good, about 92% for a single dose, quantitatively does not depend on food intake.

Distribution. The general bioavailability is 40–45%, which is associated with intensive first-pass metabolism in the liver. Venlafaxine and EFA bind to human plasma proteins by 27 and 30%, respectively; they both pass into breast milk. Venlafaxine and EFA have linear kinetics over the 75–450 mg venlafaxine daily dose range. Tmax in blood plasma of venlafaxine and EFA - 2 and 3 hours, respectively, after taking Venlafaxine tablets inside.

In the case of taking prolonged forms of venlafaxine, the Tvaluesmax are 5.5 and 9 hours, respectively.

T1/2 was (5 ± 2) h and (11 ± 2) h for venlafaxine and EFA, respectively.

Css for venlafaxine and EFA is achieved after 3 days of repeated administration of therapeutic doses.

Metabolism. It is metabolized mainly in the liver with the participation of the isoenzyme CYP2D6 to the only pharmacologically active metabolite (EFA), as well as to the inactive metabolite of N-desmethylvenlafaxine.

Venlafaxine is a weak inhibitor of the isoenzyme CYP2D6, does not inhibit CYP1A2, CYP2C9 or CYP3A4.

Excretion. It is excreted mainly by the kidneys: approximately 87% of the taken single dose is excreted in the urine within 48 hours (5% - unchanged, 29% - in the form of unconjugated EFA, 26% - in the form of conjugated EFA, 27% - in the form of other inactive metabolites) , and after 72 hours 92% of the drug is excreted by the kidneys.

The mean ± SD for the plasma clearance of venlafaxine and EFA is (1.3 ± 0.6) and (0.4 ± 0.2) L / h / kg, respectively; apparent T1/2 (5 ± 2) and (11 ± 2) h, respectively; apparent Vss (7.5 ± 3.7) and (5.7 ± 1.8) l / kg, respectively.

Special patient groups

The gender and age of the patient do not significantly affect the pharmacokinetic parameters of venlafaxine and EFA.

For elderly patients, special dose adjustment depending on age is not required.

In patients with low activity of the isoenzyme CYP2D6, there is no need to select individual doses. Despite the multidirectional change in concentrations taken separately, namely venlafaxine (increases) and EFA (decreases), the sum of the AUC of these two active substances does not actually change due to a decrease in the activity of the isoenzyme CYP2D6, respectively, dose adjustment is not required.

In patients withhepatic and renal insufficiency, the moderate to severemetabolism of venlafaxine and the elimination of EFA decreases, the Cmax of venlafaxine and EFA increases, and Tlengthened1/2 is. The decrease in the total clearance of venlafaxine is most pronounced in patients with Cl creatinine below 30 ml / min, as well as in patients on renal dialysis (T1/2 increases by 180% for venlafaxine and by 142% for EFA, and the clearance of both active substances decreases by about 57%). For such patients, especially those on hemodialysis, it is necessary to individually select the dose of venlafaxine and control the kinetics, taking into account the duration of treatment with this drug.

Although data for patients with severe hepatic impairment on the Child-Pugh scale are limited, it should bein mind that individual variations in pharmacokinetics, in particular drug clearance and its T1/2borne, are very diverse, which should be considered when prescribing venlafaxine to such patients. In patients with Child-Pugh class A (mild liver dysfunction) and Child-Pugh class B (moderate disturbances), the T1/ 2 of venlafaxine and EFA is approximately 2 times lengthened compared to that in healthy patients, and clearance is reduced more than half.

After oral administration, venlafaxine is well absorbed from the gastrointestinal tract. After a single dose of 25–150 mg, Cmax in blood plasma is reached within approximately 2.4 hours and is 33–172 ng / ml. After taking the drug with meals, the time to reach Cmax in blood plasma increases by 20-30 minutes, but the Cvaluesmax and absorptiondo not change.

Venlafaxine is extensively metabolized during its first passage through the liver. The main metabolite is EFA. Cmax EFA in blood plasma is reached after about 4.3 hours after administration and was 61-325 ng / ml. In the range of 75–450 mg daily doses, the pharmacokinetics of venlafaxine and EFA are linear.

Plasma protein binding of venlafaxine and EFA is 27% and 30%, respectively. With repeated administration ofCss venlafaxineand EFA are achieved within 3 days.

T1/2 of venlafaxine and EFA are 5 and 11 hours, respectively. EFA and other metabolites, as well as unchanged venlafaxine, are excreted by the kidneys.

In patients with cirrhosis of the liver, plasma concentrations of venlafaxine and EFA are increased, and the rate of their excretion is reduced. In moderate to severe renal failure (Cl creatinine <30 ml / min), the total clearance of venlafaxine and EFA decreases, and T1/2 increases.

The age and sex of the patient do not affect the pharmacokinetics of the drug.

Venlafaxine is well absorbed from the gastrointestinal tract. After a single dose of 25–150 mg Cmax in blood plasma reaches 33–172 ng / ml for about 2.4 hours. Undergoes intensive metabolism during the “first pass” through the liver. Its main metabolite is O-desmethylvenlafaxine (EFA). T1/2 of venlafaxine and EFA is 5 and 11 hours, respectively. Cmax EFA in blood plasma (61-325 ng / ml) is achieved approximately 4.3 hours after administration. The binding of venlafaxine and EFA with blood plasma proteins is 27 and 30%, respectively. EFA and other metabolites, as well as unmetabolized venlafaxine, are excreted by the kidneys. With repeated administration, equilibrium concentrations of venlafaxine and EFA are reached within 3 days. Venlafaxine and EFA have linear kinetics in the 75–450 mg daily dose range. After taking the drug with meals, the time to reach the maximum concentration in the blood plasma increases by 20-30 minutes, but the values ​​of the maximum concentration and absorption do not change.

In patients with cirrhosis of the liver, plasma concentrations of venlafaxine and EFA are increased, and the rate of their excretion is reduced. In moderate or severe renal failure, the total clearance of venlafaxine and EFA decreases and the half-life is lengthened. Decrease in total clearance is mainly observed in patients with Cl creatinine below 30 ml / min. The age and sex of the patient do not affect the pharmacokinetics of the drug.

Method of administration and dosage of Effexor XR

Inside, with meals. Each capsule should be swallowed whole and washed down with a liquid. Capsules must not be divided, crushed, chewed, or placed in water. The daily dose should be taken in one dose (morning or evening), each time at approximately the same time.

Depression. The recommended starting dose is 75 mg once a day.

If, according to the doctor, a higher dose is needed (severe depressive disorder or other conditions requiring hospital treatment), you can immediately prescribe 150 mg once a day. Subsequently, the daily dose can be increased by 75 mg at intervals of 2 weeks or more (but not more often than after 4 days), until the desired therapeutic effect is achieved. The maximum daily dose is 350 mg.

After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

Supportive care and prevention of relapse. Treatment for depression should be continued for at least 6 months. For stabilization therapy, and therapy to prevent relapse or new episodes of depression, doses that have been demonstrated to be effective are usually used. The doctor should regularly (at least once every 3 months) monitor the effectiveness of long-term therapy with Effexor XR®.

Transfer of patients from Effexor XRtablets®. Patients taking Effexor XRswitched to® tablets can beextended-release capsules with an equivalent dose once a day. However, individual dose adjustment may be required.

Renal failure With mild renal failure (GFR more than 30 ml / min), dosage adjustment is not required. In moderate renal failure (GFR 10-30 ml / min), the dose should be reduced by 50%. Due to the lengthening T1/2 of venlafaxine and EFA, such patients should take the entire dose once a day. It is not recommended to use venlafaxine in severe renal failure (GFR less than 10 ml / min), as reliable data on such therapy are not available. Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completing hemodialysis.

Liver failure. With mild hepatic impairment (PT less than 14 s), no dosage adjustment is required. With moderate hepatic impairment (PT from 14 to 18 s), the dose should be reduced by 50%. It is not recommended to use venlafaxine for severe hepatic impairment, as reliable data on such therapy are not available.

Elderly patients. By itself, the elderly patient's age does not require a dose change, however (as with the appointment of other drugs), caution is required in the treatment of elderly patients, for example, due to the possibility of renal dysfunction. The lowest effective dose should be used. When the dose is increased, the patient should be under close medical supervision.

Children and adolescents (under the age of 18). The safety and efficacy of venlafaxine in children and adolescents under 18 years of age has not been established.

Cancel Effexor XR®. As with treatment with other antidepressants, abrupt withdrawal of (especially high doses) venlafaxine may cause withdrawal symptoms (see "Side Effects" and "Special Instructions"). Therefore, before completely discontinuing the drug, a gradual dose reduction is recommended. If high doses have been used for more than 6 weeks, it is recommended to reduce doses for at least 2 weeks. The length of the period required to reduce the dose depends on the size of the dose, the duration of therapy, and the patient's response.

Inside, during meals, preferably at the same time, without chewing and drinking liquid.

The recommended starting dose is 75 mg in 2 divided doses daily (37.5 mg 2 times a day). Depending on tolerance and effectiveness, the dose may be gradually increased to 150 mg / day. If necessary, the dose is increased to 225 mg / day. An increase in the dose by 75 mg / day can be made at intervals of 2 weeks or more, in case of clinical need, due to the severity of the symptoms, it is possible to increase the dose in a shorter time, but not less than 4 days. Higher doses (up to a maximum daily dose of 375 mg / day in 2-3 divided doses) require inpatient observation of patients. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

Supportive care and prevention of relapse. Supportive treatment can last 6 months or more. The minimum effective dose used in the treatment of a depressive episode is prescribed.

Renal failure In mild renal failure (GFR> 30 ml / min), no dosage adjustment is required. In moderate renal impairment (GFR 10-30 ml / min), the dose should be reduced by 25-50%. Due to the prolonged T1/2 of venlafaxine and its active metabolite (EFA), such patients should take the entire dose once a day. Venlafaxine is not recommended for severe renal impairment (GFR <10 ml / min), as no reliable data are available on this therapy. With hemodialysis, the daily dose should be reduced by 50%, the drug should be taken after the end of the hemodialysis session.

Liver failure. With mild hepatic impairment (PT <14 s), no dosage adjustment is required. With moderate hepatic impairment (PT from 14 to 18 s), the daily dose should be reduced by 50% or more. It is not recommended to use venlafaxine for severe hepatic impairment, as there is no reliable data on such therapy.

Elderly patients. The elderly age of the patient in the absence of any acute and chronic diseases does not require a change in the dose, however (as with the appointment of other drugs), caution is required when treating elderly patients. Elderly patients should be given the lowest effective dose. When the dose is increased, the patient should be under close medical supervision.

drug

Discontinuation of theDiscontinuation of the drug should be carried out gradually to minimize the risk associated with drug withdrawal. With a course of treatment for 6 weeks or more, the period of gradual withdrawal of the drug should be at least 2 weeks and depend on the dose, duration of therapy and the individual characteristics of the patient.

Inside, during meals, preferably at the same time, without chewing and drinking liquid.

For the treatment of depression, the recommended starting dose of Effexor XR® is 37.5 mg 2 times a day. If after several weeks of treatment there is no significant improvement, the dose can be increased to 150 mg / day - 75 mg 2 times a day.

If it is necessary to use the drug in a higher dose for severe depressive disorder or other conditions requiring hospital treatment, you can immediately prescribe 75 mg 2 times a day. Thereafter, 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 Effexor XR® is 375 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

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

With renal failure of mild severity (glomerular filtration rate more than 30 ml / min), correction of the dosage regimen is not required.

In case of moderate renal failure (glomerular filtration rate 10–30 ml / min), the dose should be reduced by 25–50%. Due to the prolongation of T1/2 of venlafaxine and its active metabolite, such patients should take the entire dose once a day.

In severe renal impairment (glomerular filtration rate less than 10 ml / min), the use of Effexor XR® is not recommended, as experience with such therapy is limited.

Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completing hemodialysis.

With mild hepatic impairment (PT less than 14 s), no dosage adjustment is required.

With moderate hepatic impairment (PT from 14 to 18 s), the dose should be reduced by 50%.

In severe hepatic insufficiency application Effexor XRdrug® is not recommended because such therapy is limited experience.

Elderly patients do not need dose adjustment, however (as with the appointment of other drugs), care must be taken in treatment, for example, due to the possibility of impaired renal function. Therefore, in elderly patients, the lowest effective dose of the drug should be used; close medical supervision is indicated if necessary to increase the dose.

Discontinuation of Effexor XR®

At the end of treatment, it is recommended to gradually reduce the dose. When used in a dose equal to or exceeding 75 mg for 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 a course of more than 6 weeks, the period required to completely stop taking the drug is at least 2 weeks. The appearance of symptoms of a relapse of the disease during the period of discontinuation of Effexor XR® requires an initial dose of the drug or a more gradual and prolonged reduction.

Inside, without chewing, with a liquid, preferably at the same time, during meals.

The recommended starting dose is 75 mg in 2 divided doses (37.5 mg each) daily. The recommended dosage for moderate depression is 225 mg / day in 3 divided doses. If necessary, the dosage can be increased at intervals of at least 4 days by 75 mg / day. If no significant improvement is observed after several weeks of treatment, the daily dose can be increased to 150 mg (2 x 75 mg per day). If, according to the doctor, a higher dose is needed (major depressive disorder or other conditions requiring hospital treatment), 150 mg can be prescribed immediately in two divided doses (2 × 75 mg per day). Thereafter, 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 Ephevelon is 375 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

Supportive therapy and prevention of relapse: Supportive treatment may last 6 months or more. The minimum effective dose used in the treatment of a depressive episode is prescribed.

Renal failure: with mild renal failure (glomerular filtration rate (GFR) more than 30 ml / min), no dosage adjustment is required. With moderate renal failure (GFR - 10-30 ml / min), the dose should be reduced by 25-50%. Due to the lengthening half-life of venlafaxine and its active metabolite (EFA), such patients should take the entire dose once a day. It is not recommended to use venlafaxine in severe renal failure (GFR less than 10 ml / min), as reliable data on such therapy are not available. Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completing hemodialysis.

Liver failure: with mild hepatic failure (prothrombin time (PT) less than 14 s), no dosage adjustment is required. With moderate hepatic impairment (PT from 14 to 18 s), the dose should be reduced by 50%. It is not recommended to use venlafaxine for severe hepatic impairment, as reliable data on such therapy are not available.

Elderly patients: the old age of the patient itself does not require a dose change, however (as with the appointment 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 increased, the patient should be under close medical supervision.

Discontinuation of the drug: at the end of taking the drug Efevelon, it is recommended to gradually reduce the dosage of the drug, at least for 1 week, and monitor the patient's condition in order to minimize the risk associated with drug withdrawal (see below).

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

Overdose

Symptoms: ECG changes (prolongation of the QT interval, blockade of the bundle branch, expansion of the QRS complex), sinus or ventricular tachycardia, bradycardia, arterial hypotension, convulsive states, depression of consciousness (decreased level of wakefulness). In case of an overdose of venlafaxine while taking it with alcohol and / or other psychotropic drugs, death has been reported.

Treatment: symptomatic. No specific antidotes are known. Continuous monitoring of vital functions (respiration and circulation) is recommended. Appointment of activated carbon to reduce the absorption of the drug. Induction of vomiting is not recommended due to the risk of aspiration. Venlafaxine and EFA are not cleared by dialysis.

Symptoms: impaired consciousness (from drowsiness to coma), agitation, possible vomiting, diarrhea; tremor, decrease or (mild) increase in blood pressure, dizziness, mydriasis, convulsive conditions, sinus or ventricular tachycardia or bradycardia; ECG changes (lengthening of the QT interval, bundle branch block, expansion of the QRS complex). Post-marketing experience indicates that the most common overdose of venlafaxine occurred while taking alcohol and / or other psychotropic drugs. There are repeated reports of deaths. Published literary sources on retrospective studies of venlafaxine overdose report that such an increased risk of fatal outcomes may be inherent in venlafaxine when compared with the antidepressants of the SSRI group available in the medical circulation, but this risk is lower than the risk inherent in tricyclic antidepressants. Epidemiological studies have shown that those patients treated with venlafaxine have a greater burden of suicide risk than those treated with SSRIs (other than venlafaxine). However, it remains unclear to what extent such high rates of deaths (due to venlafaxine overdose) are due to the toxic properties of the drug itself or to the special characteristics of the group of patients treated with venlafaxine. According to clinical experience, it is recommended to prescribe the minimum possible amount in prescriptions for venlafaxine, sufficient only until the patient's next visit to the doctor, in order to reduce the risk of deliberate overdose (see also "Special instructions").

Treatment: symptomatic and supportive therapy is performed. No specific antidotes are known. Continuous monitoring of vital functions (respiration, circulation and heart rate) is recommended. In case of an overdose, immediate gastric lavage is recommended, the appointment of activated carbon to reduce the absorption of the drug. It is not recommended to induce vomiting at risk of aspiration of vomit. Forced diuresis, dialysis, blood transfusion are ineffective.

Symptoms (often occurring while taking ethanol): dizziness, decreased blood pressure, ECG changes (lengthening of the QT interval, bundle branch block, expansion of the QRS complex), sinus and ventricular tachycardia or bradycardia, impaired consciousness (from drowsiness to coma), convulsions; death is possible.

Treatment: symptomatic, under continuous monitoring of the ECG and the functions of vital organs. Induction of vomiting is not recommended due to the risk of aspiration. It is recommended to maintain an airway, adequate pulmonary ventilation and oxygenation. Hemodialysis is ineffective - venlafaxine and EFA are not cleared during dialysis. No specific antidotes are known.

Symptoms: ECG changes (prolongation of the QT interval, bundle branch block, expansion of the QRS complex), sinus or ventricular tachycardia, bradycardia, hypotension, convulsive states, altered consciousness (decreased wakefulness). Overdose of venlafaxine while taking it with alcohol and / or other psychotropic drugs has been reported as fatal.

Treatment: symptomatic. No specific antidotes are known. Continuous monitoring of vital functions (respiration and circulation) is recommended. Appointment of activated carbon to reduce the absorption of the drug. Induction of vomiting is not recommended due to the risk of aspiration. Venlafaxine and EFA are not cleared by dialysis.

Interaction

The simultaneous use of MAO inhibitors and venlafaxine is contraindicated. Youtaking Effexor XR® can startat least 14 days after the end of MAO inhibitor therapy. If a reversible MAO inhibitor (moclobemide) was used, this interval may be shorter (24 hours). MAO inhibitor therapy can begin at least 7 days after cancellation Effexor XR®formulation.

Concomitant use of venlafaxine with lithium may increase the level of the latter.

With simultaneous use with imipramine, the pharmacokinetics of venlafaxine and EFA do not change. At the same time, their simultaneous use enhances the effects of desipramine, the main metabolite of imipramine, and its other metabolite, 2-OH-imipramine, although the clinical significance of this phenomenon is unknown.

Haloperidol: Combined use increases blood levels of haloperidol and enhances its effects.

With simultaneous use with diazepam, the pharmacokinetics of drugs and their main metabolites does not change significantly. Also, no effect on the psychomotor and psychometric effects of diazepam was found.

With simultaneous use with clozapine, an increase in its level in blood plasma and the development of side effects (for example, seizures) can be observed.

With simultaneous use with risperidone (despite an increase in risperidone AUC), the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) does not change significantly.

The decrease in mental and physical activity under the influence of alcohol did not increase after taking venlafaxine. Despite this, as with other drugs that affect the central nervous system, alcoholic beverages are not recommended during venlafaxine therapy.

While taking venlafaxine, special care should be taken with electroconvulsive therapy, because there is no experience with venlafaxine under these conditions.

Medicines metabolized by cytochrome P450 isoenzymes: the cytochrome P450 enzyme CYP2D6 converts venlafaxine into an active metabolite of EFA. Unlike many other antidepressants, the dose of venlafaxine may not be reduced when administered concomitantly with drugs that suppress CYP2D6 activity, or in patients with a genetically determined decrease in CYP2D6 activity, since the total concentration of venlafaxine and EFA will not change.

The main route of excretion of venlafaxine involves metabolism involving CYP2D6 and CYP3A4; therefore, special care should be taken when prescribing venlafaxine in combination with drugs that inhibit both of these enzymes. Such drug interactions have not yet been investigated.

Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not suppress the activity of isoenzymes CYP1A2, CYP2C9 and CYP3A4; therefore, one should not expect its interaction with other drugs, in the metabolism of which these liver enzymes are involved.

Cimetidine inhibits the first pass metabolism 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 with impaired liver function).

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

Plasma protein-bound drugs: Plasma protein binding is 27% for venlafaxine and 30% for EFA, so protein-bound drug interactions should not be expected.

When taken simultaneously with warfarin, the anticoagulant effect of the latter can increase, while the PT is lengthened and the MHO increases.

When taken simultaneously with indinavir, the pharmacokinetics of indinavir changes (with a 28% decrease in AUC and a 36% decrease in Cmax), and the pharmacokinetics of venlafaxine and EFA do not change. However, the clinical significance of this effect is unknown.

Venlafaxine, itself not having an increased bond with blood plasma proteins, practically does not increase the concentration of simultaneously taken drugs, which are characterized by a high bond with plasma proteins. No clinically significant interaction with antihypertensive drugs (including beta-blockers, ACE inhibitors, diuretics) and antidiabetic drugs was found.

Caution should be exercised when coadministered with other drugs that affect the central nervous system, since the interaction of venlafaxine with such drugs has not been studied.

MAO inhibitors. The simultaneous use of venlafaxine with MAO inhibitors, as well as within 14 days after their withdrawal, is contraindicated (the risk of severe side effects up to death is possible). MAO inhibitor therapy can be prescribed at least 7 days after discontinuation of Venlafaxine. Venflaxin should be discontinued at least 7 days before starting reversible selective MAO inhibitors (moclobemide). Poorly reversible and non-selective MAO inhibitor linezolid (antimicrobial drug) and methylene blue (IV dosage form) are also not recommended for concomitant use with venlafaxine.

Serotonergic drugs. Caution should be exercised with the simultaneous use of drugs that affect the serotonergic transmission of drugs, such as triptans (including sumatriptan, zolmitriptan), SSRIs, SNRIs (prolonged convulsions have been reported), tricyclic antidepressants, lithium, sibutramine or fentanyl (including including its analogs - dextromethorphan, tramadol), as well as an excess of sources of tryptophan due to the increased potential risk of serotonin syndrome.

Alcohol. Alcohol should be completely avoided during venlafaxine treatment. Alcohol increases the psychomotor impairments that venlafaxine can cause.

Lithium. Lithium preparations do not significantly affect the pharmacokinetics of venlafaxine.

Diazepam. There was no evidence of an effect of orally administered diazepam on the pharmacokinetics of venlafaxine and EFA, and, conversely, venlafaxine did not alter the pharmacokinetics of diazepam and its metabolite desmethyldiazepam. In addition, the prescription of both of these drugs does not impair the psychomotor effects and psychometric parameters induced by diazepam.

Cimetidine. The simultaneous administration of cimetidine and venlafaxine led to a metabolic delay during the first passage of venlafaxine through the liver. The oral clearance of venlafaxine decreased by 43%, while the AUC and Cmax of the drug increased by 60%. However, this impact has not been seen for EFA. Since the total activity of venlafaxine and EFA is expected to increase only marginally, no dose adjustment will be required for most routine patients. However, in patients with existing (identified) hypertension, elderly patients, and those with impaired liver or kidney function, the dose of venlafaxine may be adjusted.

Haloperidol. In a study where venlafaxine was administered at stage Css at a dose of 150 mg / day, there was a 42% decrease in total clearance of oral haloperidol after a 2 mg oral dose; the AUC increased by 70%, and Cmax - by 88%, while the T1/2 of haloperidol did not change. This should be considered in order to select the correct dose of haloperidol.

Imipramine. Venlafaxine does not impair the pharmacokinetics of imipramine and 2-hydroxyimipramine. However, the AUC, Cmax and Cmin of desipramine (the active metabolite of imipramine) increased by approximately 35% while taking venlafaxine. The concentration of 2-hydroxydesipramine also increases 2.5 or 4.5 times (depending on the dose of venlafaxine: 37.5 mg or 75 mg 2 times a day), but the clinical significance of this fact is unknown.

Metoprolol. With the simultaneous use of metoprolol and venlafaxine, care should be taken, because due to pharmacokinetic interaction, the concentration of metoprolol in the blood plasma increases by about 30–40%, without changing the concentration of its active metabolite, alpha-hydroxymetoprolol. The clinical significance of this interaction has not been studied. Metoprolol does not affect the AUC of venlafaxine and EFA.

Risperidone. With simultaneous use with risperidone (despite an increase in risperidone AUC), the pharmacokinetics of a pair of active molecules (risperidone and 9-hydroxyrisperidone) does not significantly change when combined with venlafaxine.

Clozapine. In the course of a post-marketing study of venlafaxine, it was found that when used simultaneously with clozapine, its concentration in blood plasma increases. This was manifested by an increase in the side effects of clozapine, especially with regard to the frequency of seizures.

Indinavir. With simultaneous use, the pharmacokinetics of indinavir changes (AUC decreases by 28%, and Cmax decreases by 36%). No changes in the pharmacokinetics of venlafaxine have been observed. The clinical significance of this fact is unknown.

Ketoconazole. A pharmacokinetic study in combination with ketoconazole showed an increase in plasma concentrations of venlafaxine and EFA in subjects in whom the initial metabolism with the participation of the CYP2D6 isoenzyme is both good (X-Met) and poor (P-Met). In particular, the Cmax of venlafaxine increased by 26% in X-Met and by 48% in P-Met.Cvaluesmax EFAincreased by 14 and 29% in subjects X-Met and P-Met, respectively. AUC of venlafaxine increased by 21% in X-Met and by 70% in P-Met. EFA AUC values ​​increased by 23% and 33% in subjects X-Met and P-Met, respectively.

Drugs affecting blood clotting and platelet function (NSAIDs, acetylsalicylic acid and other anticoagulants). Serotonin released by platelets plays an important role in hemostasis (stopping bleeding). Epidemiological studies demonstrate a relationship between the use of psychotropic drugs that interfere with serotonin reuptake and the incidence of upper GI bleeding. This relationship is enhanced if NSAIDs, drugs containing acetylsalicylic acid or other anticoagulants are used simultaneously. The risk of bleeding has been shown to increase when SSRIs and SSRIs (including venlafaxine) are administered concurrently with warfarin. Patients who are prescribed warfarin should be closely monitored for PT and / or partial thromboplastin time, especially when concomitant use with venlafaxine begins or ends.

Interaction with other drugs at the level of the studied metabolism with cytochrome P450 isoenzymes. The main metabolic pathways of venlafaxine include the isoenzymes CYP2D6 and CYP3A4: the former converts venlafaxine into its active metabolite of EFA, and the latter is less important in the metabolism of venlafaxine compared to CYP2D6 and forms the product N-desmethylvenlafaxine with little pharmacological activity. Preclinical studies have shown, and then it has been confirmed clinically, that venlafaxine is a relatively weak inhibitor of CYP2D6. Therefore, even with the appointment of drugs with moderately inhibiting the activity of this enzyme (see above example with imipramine) or in the case of treatment of patients with a genetically determined decrease in CYP2D6 function, dose adjustment of venlafaxine is not required, because the total concentration of the active substance and active metabolite (venlafaxine and EFA) does not change significantly. This is a positive feature of venlafaxine when compared with other antidepressants. Caution should be exercised when coadministered with CYP2D6 inhibitors such as quinidine, paroxetine, fluoxetine, haloperidol, perphenazine, levomepromazine, because in this case, venlafaxine can potentially increase the plasma concentration of these CYP2D6 substrates. In combination with drugs that inhibit both enzymes (CYP2D6 and CYP3A4), special care is required. Such drug interactions have not yet been adequately studied, and in this case, such a drug combination is not recommended. In addition, venlafaxine does not suppress the activity of the enzymes CYP3A4, CYP1A2 and CYP2C9, therefore, no significant interaction is observed with such drugs as alprazolam, caffeine, carbamazepine, diazepam, tolbutamide, terfenadine.


Interaction with ketoconazole is described above. CYP3A3 / 4 inhibitors such as itraconazole, ritonavir can have a similar effect.

Other interactions with various concomitant therapeutic factors and food. While using venlafaxine, special care should be taken with electroconvulsive therapy. there is no experience with venlafaxine under these conditions. No significant effect of different types of food on the absorption of venlafaxine and its subsequent conversion to EFA has been identified. Foods (typically high-protein foods such as hard cheeses, fish roe, turkey) and dietary supplements and fitness diets that provide tryptophan have the potential to increase serotonin production in the body, which can increase the serotonergic side effects of venlafaxine.

Preparations containing St. John's wort. An undesirable pharmacodynamic interaction can occur when Venlafaxine is taken simultaneously with the herb St. John's wort (herb or various preparations from it), such a combination is not recommended.

There are reports of false-positive results of an immunochromatographic rapid urine test (test strips) for phencyclidine and amphetamines in patients taking venlafaxine, even several days after the discontinuation of venlafaxine. This can be explained by the lack of specificity of this test. Only a confirmatory test in a specialized anti-doping laboratory can distinguish venlafaxine from phencyclidine and amphetamines.

To date, venlafaxine has not been shown to cause drug abuse or addiction (either in preclinical receptor affinity studies or in clinical practice).

The concomitant use of MAO inhibitors and venlafaxine is contraindicated. Venlafaxine can be started at least 14 days after the end of MAO inhibitor therapy. If a reversible MAO inhibitor (moclobemide) was used, this interval may be shorter (24 hours). MAO inhibitor therapy can be started no earlier than 7 days after discontinuation of venlafaxine.

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

With simultaneous use with imipramine, the pharmacokinetics of venlafaxine and its metabolite EFA do not change. Venlafaxine does not affect the metabolism of imipramine and its metabolite 2-hydroxyimipramine, but it increases the AUC and Cmax in plasma 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, symptoms may appear that resemble neuroleptic malignant syndrome.

Venlafaxine reduces the renal clearance of haloperidol by 42%, while the AUC and Cvaluesmax increase by 70 and 88%, respectively. The effects of haloperidol may be enhanced.

With simultaneous use with diazepam, the pharmacokinetics of drugs and their main metabolites does not change significantly.

With simultaneous use with clozapine, an increase in its level in blood plasma and the development of side effects (for example, epileptic seizures) may occur.

With simultaneous use with risperidone, despite the increase in the AUC of the drug, the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) did not significantly change.

The simultaneous intake of ethanol and venlafaxine was not accompanied by a decrease in mental and physical activity. Despite this (as in the case of other drugs that affect the central nervous system), the use of ethanol is not recommended during venlafaxine therapy.

Cimetidine inhibits the metabolism of venlafaxine during the first passage 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 with impaired liver function). In elderly patients and in patients with impaired liver function, the simultaneous use of cimetidine and venlafaxine should be carried out under medical supervision.

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

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

Venlafaxine metabolism occurs with the participation of the cytochrome P450 system, isoenzymes CYP2D6 and CYP3A4. Taking the drug with inhibitors of the CYP2D6 isoenzyme or in patients with a genetically determined decrease in the activity of the CYP2D6 isoenzyme were not accompanied by significant changes in the concentrations of the active substance and metabolite (venlafaxine and EFA), which allows not to reduce the dose of the antidepressant. However, concomitant use with inhibitors of the isoenzyme CYP3A4 is accompanied by an increase in the concentration of venlafaxine in plasma. Therefore, special care should be taken when prescribing venlafaxine with drugs that are inhibitors of the isoenzyme CYP3A4 (ketoconazole, erythromycin) or both isoenzymes (CYP2D6 and CYP3A4).

Venlafaxine is a relatively weak inhibitor of the CYP2D6 isoenzyme and does not inhibit the activity of the CYP1A2, CYP2C9 and CYP3A4 isoenzymes. In vivo studies did not reveal the effect of venlafaxine on the metabolism of alprazolam (CYP3A4 isoenzyme), caffeine (CYP1A2 isoenzyme), carbamazepine (CYP3A4 isoenzyme) and diazepam (CYP3A4 and CYP2C19 isoenzymes).

With simultaneous use with warfarin, it is possible to enhance the anticoagulant effect of the latter, while the PT is lengthened, expressed through MHO.

When taken simultaneously with indinavir, there is a decrease in the AUC value of indinavir by 28% and a decrease in its Cmax in plasma by 36%, while the pharmacokinetic parameters of venlafaxine and EFA do not change. The clinical significance of this effect is unknown.

Venlafaxine can affect the pharmacodynamics of other drugs acting at the level of the serotonergic neurotransmitter system, therefore, caution should be exercised when it is administered concomitantly with triptans, other SSRIs, and lithium drugs.

The concomitant use of MAO inhibitors and venlafaxine is contraindicated. You can start taking Efevelon at least 14 days after the end of therapy with MAO inhibitors. If a reversible MAO inhibitor (moclobemide) was used, this interval may be shorter (24 hours). Therapy with MAO inhibitors can be started at least 7 days after discontinuation of Ephevelon.

Venlafaxine does not affect the pharmacokinetics of lithium.

With simultaneous use with imipramine, the pharmacokinetics of venlafaxine and its metabolite O-desmethylvenlafaxine (EFA) does not change.

Haloperidol: the effect of the latter may be enhanced by an increase in the level of the drug in the blood when used together.

With simultaneous use with diazepam, the pharmacokinetics of drugs and their main metabolites does not change significantly. Also, no effect on the psychomotor and psychometric effects of diazepam was found.

With simultaneous use with clozapine , an increase in its level in blood plasma and the development of side effects (for example, epileptic seizures) may occur.

With simultaneous use with risperidone (despite an increase in risperidone AUC), the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) did not significantly change.

Strengthens the effect of alcohol on psychomotor reactions.

While taking venlafaxine, special care should be taken with electroconvulsive therapy, because there is no experience with venlafaxine under these conditions.

Medicines metabolized by cytochrome P450 isoenzymes: the CYP2D6 enzyme of the cytochrome P450 system converts venlafaxine to the active metabolite O-desmethylvenlafaxine (EFA). Unlike many other antidepressants, the dose of venlafaxine may not be reduced when administered simultaneously with drugs that suppress CYP2D6 activity, or in patients with a genetically determined decrease in CYP2D6 activity, since the total concentration of the active substance and metabolite (venlafaxine and EFA) will not change.

The main route of excretion of venlafaxine involves metabolism involving CYP2D6 and CYP3A4; therefore, special care should be taken when prescribing venlafaxine in combination with drugs that inhibit both of these enzymes. Such drug interactions have not yet been investigated.

Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not suppress the activity of isoenzymes CYP1A2, CYP2C9 and CYP3A4; therefore, one should not expect its interaction with other drugs, in the metabolism of which these liver enzymes are involved.

Cimetidine inhibits the “first pass” metabolism of venlafaxine and does not affect the pharmacokinetics of O-desmethylvenlafaxine. In most patients, only a slight increase in the overall pharmacological activity of venlafaxine and O-desmethylvenlafaxine is expected (more pronounced in elderly patients and with impaired liver function).

No clinically significant interactions of venlafaxine with antihypertensive drugs (including beta-blockers, ACE inhibitors, and diuretics) and antidiabetic drugs were found.

Plasma protein-bound drugs: Plasma protein binding 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.

When taken simultaneously with warfarin , the anticoagulant effect of the latter may increase.

When taken simultaneously with indinavirindinavir , the pharmacokinetics ofchanges (with a 28% decrease in AUC and a 36% decrease in Cmax), and the pharmacokinetics of venlafaxine and EFA do not change. However, the clinical significance of this effect is unknown.

Contraindications

Hypersensitivity to any component of the drug;

simultaneous administration of MAO inhibitors (see also "Interaction");

severe impairment of renal and / or liver function (glomerular filtration rate (GFR) less than 10 ml / min, PT more than 18 s);

age up to 18 years (safety and effectiveness for this age group have not been proven);

pregnancy or suspected pregnancy;

lactation period (there are insufficient data from controlled studies).

With caution: recent myocardial infarction, unstable angina pectoris, heart failure, coronary artery disease, ECG changes, incl. lengthening of the QT interval, electrolyte imbalance, arterial hypertension, tachycardia, history of convulsions, intraocular hypertension, angle-closure glaucoma, mania in history, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight.

  • hypersensitivity to venlafaxine or any of the excipients;
  • simultaneous use with MAO inhibitors (see "Interaction");
  • severe impairment of renal and / or liver function (GFR <10 ml / min);
  • pregnancy;
  • lactation period;
  • children under 18 years of age.

With care: recent myocardial infarction; unstable angina; arterial hypertension; tachycardia; a history of convulsive syndrome; increased IOP; angle-closure glaucoma; a history of manic conditions; predisposition to bleeding from the skin and mucous membranes; initially reduced body weight.

  • individual intolerance to venlafaxine and other components of the drug;
  • simultaneous administration of MAO inhibitors (see "Interaction");
  • severe impairment of renal function (Cl creatinine <10 ml / min) and / or liver;
  • age up to 18 years;
  • pregnancy;
  • lactation period.

With care: recent myocardial infarction, unstable angina pectoris; arterial hypertension; tachycardia; a history of convulsive syndrome; increased intraocular pressure, angle-closure glaucoma; a history of manic conditions; hyponatremia; hypovolemia; dehydration; concomitant use of diuretics; suicidal tendencies; predisposition to bleeding from the skin and mucous membranes; initially reduced body weight.

  • hypersensitivity;
  • simultaneous administration of MAO inhibitors (see also the section "Interaction");
  • severe impairment of renal and / or liver function (glomerular filtration rate less than 10 ml / min);
  • age up to 18 years (safety and effectiveness for this age group have not been proven);
  • established pregnancy or suspected pregnancy;
  • period of breastfeeding.

With care:

  • recent myocardial infarction, unstable angina pectoris;
  • arterial hypertension;
  • tachycardia;
  • a history of convulsive syndrome;
  • increased intraocular pressure, angle-closure glaucoma;
  • a history of manic conditions;
  • predisposition to bleeding from the skin and mucous membranes;
  • initially reduced body weight.

Side effects

Most of the side effects listed below are dose dependent. With long-term treatment, the severity and frequency of most of these effects is reduced, and there is no need to cancel therapy.

In decreasing order of frequency: often - <1/10 and> 1/100; infrequently - <1/100 and> 1/1000; rarely - <1/1000; very rarely - <1/10000.

General symptoms: weakness, fatigue, headache, abdominal pain, chills, fever.

From the gastrointestinal tract: decreased appetite, constipation, nausea, vomiting, dry mouth; infrequently - bruxism, a reversible increase in the activity of liver enzymes; rarely - gastrointestinal bleeding; very rarely - pancreatitis.

From the nervous system: dizziness, insomnia, agitation, drowsiness; often - unusual dreams, anxiety, confusion, increased muscle tone, paresthesia, tremor; infrequently - apathy, hallucinations, myoclonus; rarely - ataxia, speech disorders, incl. dysarthria, mania or hypomania (see "Special instructions"), manifestations resembling neuroleptic malignant syndrome, seizures (see "Special instructions"), serotonergic syndrome; very rarely - delirium, extrapyramidal disorders, incl. dyskinesia and dystonia, tardive dyskinesia, psychomotor agitation / akathisia (see "Special instructions").

From the CCC: arterial hypertension, dilation of blood vessels (hot flushes), heart palpitations; infrequently - orthostatic hypotension, fainting, tachycardia; very rarely - pirouette-type arrhythmia, lengthening of the QT interval, ventricular tachycardia, ventricular fibrillation.

From the senses: accommodation disturbances, mydriasis, visual impairment, tinnitus; infrequently - a violation of taste.

From the hematopoietic system: infrequently - hemorrhages in the skin (ecchymosis) and mucous membranes; rarely - thrombocytopenia, prolonged bleeding time; very rarely - agranulocytosis, aplastic anemia, neutropenia, pancytopenia.

On the part of the skin: sweating, itching and rash; infrequently - photosensitivity reactions, angioedema, maculopapular rashes, urticaria; rarely - alopecia, erythema multiforme, Stevens-Johnson syndrome.

From the genitourinary system: ejaculation, erection disorders, anorgasmia; infrequently - decreased libido, menstrual irregularities, menorrhagia, urinary retention; rarely - galactorrhea.

From the side of metabolism: increased serum cholesterol levels, decreased body weight; infrequently - hyponatremia, syndrome of insufficient secretion of ADH, impaired liver function tests; rarely - hepatitis; very rarely - an increase in the level of prolactin.

Musculoskeletal system: arthralgia, myalgia; infrequently - muscle spasm; very rarely - rhabdomyolysis.

The following side effects were observed in children: abdominal pain, chest pain, tachycardia, refusal to eat, weight loss, constipation, nausea, ecchymosis, epistaxis, mydriasis, myalgia, dizziness, emotional lability, tremors, hostility, and suicidal thoughts.

After abrupt withdrawal of venlafaxine or a decrease in its dose, the following may occur: fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, anxiety, disorientation, hypomania, paresthesia, sweating. These symptoms are usually mild and go away without treatment. Because of the likelihood of these symptoms, it is very important to gradually reduce the dose of the drug (like any other antidepressant), especially after taking high doses. The length of the period required to reduce the dose depends on the size of the dose, the duration of therapy, and the individual sensitivity of the patient.

Frequency of side effects: very often - ≥1 / 10; often - ≥1 / 100 to <1/10; infrequently - ≥1 / 1000 to <1/100; rarely - ≥1 / 10000 to <1/1000; very rarely - <1/10000; the frequency has not been established (there are currently no data on the prevalence of adverse reactions).

General symptoms: often - weakness, fatigue, chills; infrequently - Quincke's edema, photosensitivity reactions; frequency not established - anaphylactic reactions.

From the nervous system: very often - dry mouth, headache; often - unusual dreams, decreased libido, dizziness, insomnia, increased excitability, paresthesia, stupor, confusion, depersonalization, increased muscle tone, tremor; infrequently - apathy, agitation, hallucinations, myoclonus, impaired coordination of movements and balance; rarely - akathisia, psychomotor agitation, epileptic seizures, manic reactions; frequency not established - dizziness, neuroleptic malignant syndrome (NMS), serotonin syndrome, delirium, extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, suicidal thoughts and behavior, aggression.

Co side of the digestive tract: very often - nausea; often - decreased appetite (anorexia), constipation, vomiting; infrequently - bruxism, diarrhea; rarely - hepatitis; frequency not established - pancreatitis.

From the respiratory system: often - yawning, bronchitis, shortness of breath; rarely - interstitial lung disease (ILD) and eosinophilic pneumonia, chest pain.

From the CCC: often - arterial hypertension, skin hyperemia; infrequently - postural hypotension, tachycardia, syncope; frequency not established - hypotension, prolongation of the QT interval, ventricular fibrillation, ventricular tachycardia (including bidirectional tachycardia).

From the hematopoietic system: infrequently - hemorrhages in the skin (ecchymosis), gastrointestinal bleeding; the frequency is not established - hemorrhages in the mucous membranes, lengthening of bleeding time, thrombocytopenia, pathological changes in the blood (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia).

From the side of metabolism: often - an increase in the level of Xc in the blood serum, a decrease in body weight; infrequently - an increase in body weight; very rarely - an increase in the content of prolactin; the frequency is not established - changes in laboratory tests of liver function, hepatitis, hyponatremia, syndrome of insufficient secretion of ADH.

On the part of the genitourinary system: often - ejaculation / orgasm disorders in men, erectile dysfunction (impotence), anorgasmia, dysuric disorders (mainly difficulties at the beginning of urination), pollakiuria, menstrual irregularities associated with increased bleeding or increased irregular bleeding (menorrhagia, metrorrhagia); infrequently - orgasm disorders in women, urinary retention; rarely - urinary incontinence.

From the senses: often - accommodation disorders, mydriasis, visual impairment; infrequently - a violation of taste, noise or ringing in the ears; frequency not established - angle-closure glaucoma.

From the side of the skin: very often - sweating; infrequently - alopecia, a rapidly passing rash; frequency not established - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus, urticaria.

From the side of the musculoskeletal system: the frequency has not been established - rhabdomyolysis.

When you stop taking venlafaxine, abruptly cancel or reduce the dose, you may experience symptoms that refer to the so-called. withdrawal syndrome: increased fatigue, asthenia, headache, dizziness, sleep disturbances (drowsiness or insomnia, difficulty falling asleep, the appearance of unusual dreams), hypomania, anxiety, agitation (increased nervous irritability and irritability), confusion, paresthesias (incl. spontaneously arising unpleasant sensation of numbness, tingling, burning, crawling creeps), increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are mild and do not require treatment).

Side effects are classified according to the following frequency: very common (at least 10%); often (at least 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 rare (less than 0.01%, including isolated cases).

Most of the side effects listed below are dose dependent. With prolonged treatment, their severity and frequency decreases, and the need to cancel therapy usually does not arise.

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

From the side of metabolism: often - an increase in the level of cholesterol in the blood serum (especially after prolonged use or taking the drug in high doses), a decrease or increase in body weight; infrequently - hyponatremia, syndrome of insufficient secretion of ADH; in some cases - an increase in the level of blood plasma prolactin.

From the CCC: often - increased blood pressure, hyperemia of the skin; infrequently - decreased blood pressure, postural hypotension, fainting, arrhythmia, tachycardia; very rarely - arrhythmia of the pirouette type, prolongation of the QT interval, ventricular tachycardia, ventricular fibrillation.

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

From the side of mental status: the frequency has not been established - depression, the appearance of suicidal thoughts and suicidal behavior during therapy and after drug withdrawal.

From the hematopoietic and lymphatic system: infrequently - hemorrhages in the skin (ecchymosis) and mucous membranes, thrombocytopenia, prolonged bleeding time, hemorrhagic syndrome; in some cases - agranulocytosis, aplastic anemia, neutropenia and pancytopenia.

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

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

From the senses: often - accommodation disorders, mydriasis, visual impairment, noise or ringing in the ears; infrequently - disturbances in taste.

On the part of the skin and its appendages: often - increased sweating (including nighttime); 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, urticaria; rarely - exudative erythema multiforme, Stevens-Johnson syndrome; in some cases - anaphylactic reactions.

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

After abrupt withdrawal of venlafaxine or dose reduction, increased 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, tremors, paresthesias, excessive sweating, tachycardia, convulsions, ringing or tinnitus, refusal to eat. To prevent the development of withdrawal symptoms, it is very important to gradually reduce the dose of the drug, especially after taking in high doses.

Most of the side effects listed below are dose dependent. With long-term treatment, the severity and frequency of most of these effects decreases, the need to cancel therapy does not arise.

In decreasing order of frequency: often - ≥1%, sometimes - ≥0.1– <1%, rarely - ≥0.01– <0.1%, very rarely - <0.01%.

General symptoms: weakness, fatigue.

From the gastrointestinal tract: decreased appetite, constipation, nausea, vomiting, dry mouth, rarely - hepatitis.

From the side of metabolism: increased serum cholesterol levels, decreased body weight; sometimes - 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; sometimes - postural hypotension, tachycardia.

From the nervous system: unusual dreams, dizziness, insomnia, irritability, paresthesia, stupor, increased muscle tone, tremor; sometimes - apathy, hallucinations, muscle spasms, serotonin syndrome; rarely - epileptic seizures, manic reactions, and symptoms resembling neuroleptic malignant syndrome.

From the genitourinary system: disorders of ejaculation, erection, anorgasmia, dysuric disorders (mainly - difficulties at the beginning of urination); sometimes - decreased libido, menorrhagia, urinary retention.

From the senses: accommodation disturbances, mydriasis, visual impairment; sometimes - a violation of taste.

On the part of the skin: sweating; sometimes - photosensitivity reactions; rarely - erythema multiforme, Stevens-Johnson syndrome.

From the hematopoietic system and blood coagulation: sometimes - thrombocytopenia; hemorrhages in the skin (ecchymosis) and mucous membranes, rarely - lengthening the bleeding time.

Hypersensitivity reactions: sometimes - skin rash; very rarely - anaphylactic reactions.

After abrupt withdrawal of venlafaxine or a decrease in its dose, the following may occur: fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, irritability, disorientation, hypomania, paresthesia, sweating. These symptoms are usually mild and go away without treatment. Because of the likelihood of these symptoms, it is very important to gradually taper the dose.