Antidepressant. Reuptake inhibitor of serotonin and norepinephrine.
Venlafaxine hydrochloride - white or almost white crystalline solid. Solubility in water 572 mg / ml. Octanol-water partition coefficient is 0,43. Molecular weight - 313,87.
Venlafaxine: pharmachologic effect
According to Physicians Desk Reference (2004), Venlafaxine hydrochloride form immediate release tablets is indicated for the treatment of depression. Venlafaxine hydrochloride form The modified-release capsules is indicated for the treatment of depression, generalized anxiety disorder and social phobia.
Hypersensitivity, simultaneous MAO inhibitors (cm. Precautions).
Venlafaxine: restrictions on use
Recent myocardial infarction and unstable angina, changes in blood pressure, increased intraocular pressure, and angle-closure glaucoma, mania in history, initially underweight, renal / hepatic insufficiency, Age to 18 years (Safety and efficacy have not been established).
Venlafaxine: use during pregnancy and lactation
In pregnancy, the use is possible only in case of emergency (adequate and well-controlled studies of the safety of use in pregnant women were not conducted).
Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)
Teratogenic effects. Venlafaxine did not cause malformations in the offspring of rats and rabbits, get it in doses, to 11 time (rats) or 12 time (Rabbits) exceeding MRDC (calculated in mg/kg), or in 2,5 times (rats) and 4 times (Rabbits) above MRDC (calculated in mg/m2). However, in rats (If venlafaxine began to give during pregnancy and continued until the end of the nursing period) It showed a decrease in body weight babies, increase in the number of stillborn pups, increase in pup mortality in the first 5 feeding days. The cause of these deaths is unknown, These effects were observed at doses 10 time (mg / kg) or 2,5 times (mg / m2) exceeds MRDC. There was no effect on mortality of young rats at doses, exceeding MRDC in 1,4 times (mg / kg) or in 0,25 MRDC times (mg / m2).
Nonteratogenic effects. If venlafaxine is used until or immediately before the birth, you must consider the possibility of withdrawal reactions (discontinuation effects) newborn.
The effect of venlafaxine hydrochloride 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 children, breastfed, nursing mothers should stop breast-feeding or, or use of drugs (in accordance with the importance PM Mother).
Venlafaxine: side effects
Immediate Release Tablets
Side effects, associated with discontinuation of treatment
19% patients (537/2897) depression, treated with venlafaxine, in research Phases 2 and Phase 3 discontinued therapy due to the occurrence of side effects. The most common effects (≥1%), yavivshimisya cause discontinuation of therapy and treated as due to taking drugs (ie. observed approximately 2 times or more frequently when receiving venlafaxine versus placebo), They were as follows (in brackets the percentage placebo): drowsiness 3% (1%), insomnia 3% (1%), dizziness 3% (<1%), headache 3% (1%), alarm 2% (1%), nervousness 2% (<1%), asthenia 2% (<1%); dry mouth 2% (<1%), nausea 6% (1%), abnormal ejaculation 3% (<1%), Sweating 2% (<1%).
Side effects, observed in controlled trials
The most common side effects, associated with the reception of venlafaxine hydrochloride (the frequency of occurrence 5% and more), not the same as the frequency of occurrence in the placebo group, ie. when receiving venlafaxine hydrochloride were observed in at least 2 times more likely, than placebo (cm. Table. 1), bыli asthenia, Sweating, nausea, constipation, anorexia, vomiting, drowsiness, dry mouth, dizziness, nervousness, alarm, tremor, blurred vision, abnormal ejaculation / orgasm and impotence in men.
Side effects, observed with a frequency ≥1% patients, treated with venlafaxine hydrochloride (Table 1). In the table 1 presents side effects, marked in patients, receiving venlafaxine hydrochloride in the form of tablets in doses of 75-375 mg/day when conducting short term tests (4- 8-week). These effects were observed at a frequency of ≥1% and greater than placebo in frequency. The table shows the percentage of patients in each group, who had at least one case of a single side effect of the treatment period. Side effects are grouped using a standard terminology dictionary COSTART.
Side effects, observed in the 4-8-week placebo-controlled clinical trials in patients with depression
|Body systems / Side effects||Venlafaxine (n=1033), %||Placebo (n=609), %|
Body as a Whole
|Increased blood pressure / hypertension||2||–|
|Violation of the thinking process||2||1|
|Abnormal ejaculation / orgasm||12*||-*|
|Violation of urination||2||–|
|Violation of orgasm||2**||-**|
– less 1%
Adverse effects, marked at least in 1% patients, taking venlafaxine hydrochloride, and observed with a frequency, equal to or less than placebo, They include the following: pain, incl. abdominal pain, backache, myalgia, arthralgia, flu-like symptoms, fever, heartbeat, increased appetite, amnesia, gipesteziya, rhinitis, pharyngitis, sinusitis, increased cough, dysmenorrhoea (female).
The dependence of the side effects of the dose. Assessment of the degree of severity of side effects in patients, receiving venlafaxine hydrochloride, comparative study was carried out in a fixed-dose: 75 mg / day (n=89), 225 mg / day (n=89), 375 mg / day (n=88) placebo (n=92). We consider the effect of, which occurred at a frequency 5% or more in at least one of the groups of patients, treated with venlafaxine, and observed for at least 2 times more likely, than placebo.
To assess trends in the potential "dose-side effect" test was used Cochran-Armitage with double criterion, for the level of statistical significance accepted P<0,05. The analysis shows dose response effects of certain, including the following:: chills, hypertension, anorexia, nausea, ažitaciâ, dizziness, drowsiness, tremor, zevota, Sweating, abnormal ejaculation.
Adapting to some side effects
During the 6-week treatment period, there were cases of adaptation to certain side effects (eg, dizziness and nausea), to a lesser extent, to other effects (eg, abnormal ejaculation, dry mouth).
Modified release capsule
The data, resulting in short-term placebo-controlled trials.
Side effects, associated with discontinuation of treatment
According to the results of clinical trials, nearly 11% from 357 Patients with major depressive episode, receiving venlafaxine hydrochloride, discontinued treatment because of side effects, compared to 6% from 285 patients, placebo. Patients with GAD, the comparable figure was 18% from 1381 patients (Placebo - 12% from 555), in patients with SF- 17% from 277 patients (Placebo - 5% from 274).
Side effects, that led to discontinuation of treatment and were associated with drug administration (ie. leading to discontinuation of the drug, at least in 1% patients, and meeting at least 2 times more likely to placebo), depending on the diagnosis were as follows (in brackets the percentage placebo):
in patients with depression — nausea 4% (<1%), anorexia 1% (<1%), dry mouth 1% (0%), dizziness 2% (1%), insomnia 1% (<1%), drowsiness 2% (<1%);
in patients with GAD-asthenia 3% (<1%), nausea 8% (<1%), dry mouth 2% (<%), vomiting 1% (<%), insomnia 3% (<1%), drowsiness 3% (<1%), nervousness 2% (<1%), tremor 1% (0%), Sweating 2% (<1%);
in patients with SF-fatigue 1% (<1%), headache 2% (<1%), nausea 4% (0%), dizziness 2% (0%), insomnia 3% (<1%), drowsiness 2% (<1%), alarm 1% (<1%), Sweating 1% (0%), impotence 3% (0%).
Side effects, observed in controlled trials of frequency ≥2% in patients, treated with venlafaxine hydrochloride (Table 2).
In the table 2 presents side effects, marked in patients, receiving venlafaxine hydrochloride during the placebo-controlled clinical trials in the emergency treatment of major depressive episode (to 12 Sun, a dose range from 75 to 225 mg / day), GTR (to 8 Sun, a dose range from 37,5 to 225 mg / day) and SF (to 12 Sun, a dose range from 75 to 225 mg / day). These effects were observed at a frequency ≥2% and greater than placebo in frequency. The table shows the percentage of patients in each group, who had at least one case of a single side effect of the treatment period. Side effects are grouped using a standard terminology dictionary COSTART.
The most common side effects, associated with the reception of venlafaxine hydrochloride (the frequency of occurrence 5% and more), not the same as the frequency of occurrence in the placebo group (ie. when receiving venlafaxine hydrochloride were observed in at least 2 times more likely, than placebo) in clinical trials, depending on the diagnosis, They were as follows (cm. and Table 2):
Patients with depression in all placebo-controlled trials have been observed, in particular: abnormal ejaculation, gastrointestinal disorders (nausea, dry mouth and anorexia), disorders of the central nervous system (dizziness, drowsiness, unusual dreams), Sweating. In two placebo-controlled trials, held in the USA, additionally were marked (n=192): sexual dysfunction (impotence in men, anorgasmia in women, decreased libido), gastrointestinal disorders (constipation and flatulence), disorders of the central nervous system (insomnia, nervousness and tremor), blurred vision, cardiovascular disorders (gipertenziya and vasodilation), zevota.
Patients with GAD for all placebo-controlled trials noted: sexual dysfunction (abnormal ejaculation and impotence), gastrointestinal disorders (nausea, dry mouth, anorexia, constipation), blurred vision, Sweating.
In patients with SF in both the placebo-controlled trials were marked asthenia, gastrointestinal disorders (anorexia, dry mouth, nausea), disorders of the central nervous system (alarm, insomnia, decreased libido, nervousness, drowsiness, dizziness), sexual dysfunction (abnormal ejaculation, orgasmic disorder, impotence), zevota, Sweating, blurred vision.
Side effects, observed in the placebo-controlled clinical trials in patients with depression, generalized anxiety disorder (GTR) and social phobia (SF)
|Body systems / Side Effects||Depression||GTR||SF|
|Venlafaxine (n=357), %||Placebo (n=285), %||Venlafaxine (n=1381), %||Placebo (n=555), %||Venlafaxine (n=277), %||Placebo (n=274), %|
|Body as a Whole|
|Vasodilation (mostly hot flashes)||4||2||4||2||3||1|
|Unusual dreams (mainly vivid dreams, nightmares, dream with snovideniяmi)||7||2||3||2||4||<1|
|Violation of (incl. blurred vision)||4||<1||5||<1||6||3|
|Violation of ejaculation (incl. delayed ejaculation)*||16||<1||11||<1||16||1|
|Orgasmic disorder (incl. delay orgasm, anorgazmija)**||3||<1||2||0||8||0|
– less 2%
* It recorded only in males
** It recorded only in women
It will be appreciated, that the data on adverse effects, obtained in the placebo-controlled studies, They can not be used to predict the occurrence of side effects in normal medical practice, tk. condition of the patient and other factors differ from those, that prevailed in the clinical trials. In a similar way, figures in Tables incidence of side effects (in percents) may differ from those obtained by other investigators clinical, tk. Each test drug can be performed with a different set of conditions. However, these figures give the doctor an idea of the relative contribution of the substance and other factors (non-PM), in the development of side-effects of drugs in the population.
Changes in vital signs
Immediate Release Tablets
In clinical trials revealed, that in patients receiving venlafaxine heart rate was increased by about 3 beats per minute - the mean value for all groups of patients, treated with various doses of (vs placebo, where such changes were seen). In studies with a range of doses of 200-375 mg/day (the average dose value is more 300 mg / day) heart rate was increased by an average of 2 beats per minute (vs placebo, which showed a decrease in the 1 beats per minute).
In controlled clinical trials venlafaxine was associated with the acquisition of raising Dad in the range 0.7-2.5 mm Hg. (for all groups of patients) vs placebo, where a decrease was noted in the range 0.9-dad 3.8 mm Hg. This was a dose-dependent increase in blood pressure (cm. Precautions, resistant hypertension).
Modified release capsule
In premarketingovyh placebo-controlled trials in patients with major depressive episode, receiving venlafaxine hydrochloride during a period until 12 Sun, by the end of therapy showed an increase in heart rate by an average of 2 bpm versus placebo (an increase of 1 beats per minute). Similar results were obtained in premarketingovyh placebo-controlled studies in patients with GAD (to 8 weeks of treatment). In premarketingovyh placebo-controlled studies in patients with SF, receiving venlafaxine over a period of up to 12 Sun, heart rate was increased by an average of 4 beats per minute (changes in the placebo group was observed).
Changes in laboratory parameters
According to the results of monitoring of laboratory parameters, conducted during clinical trials of venlafaxine (tablets, capsules), Statistically significant differences (vs placebo) We observed only in the level of serum cholesterol. So, in the treatment of venlafaxine (tablets) patients with depression at least 3 months of clinically significant increases in cholesterol levels have been reported in 5,3% patients compared with 0% placebo (the results of the 12-month, placebo-controlled trials).
Comparison of ECG in patients, receiving venlafaxine hydrochloride (n=769) placebo (n=450) In controlled clinical trials showed, statistically significant difference appeared only increase the heart rate in patients receiving venlafaxine.
Incompatible with MAO inhibitors (cm. Precautions).
The simultaneous use in 18 healthy volunteers cimetidine and venlafaxine in achieving equilibrium concentrations of both substances resulted in inhibition of metabolism of venlafaxine in the "first pass" through the liver, reducing clearance venlafaxine approximately 43% and the increase in AUC and Cmax on 60%, while cimetidine did not affect the pharmacokinetics of EFA (which is present in the systemic circulation at a significantly larger amount, Cem venlafaxine); general pharmacological activity of "venlafaxine EFA" increased only slightly; interaction of cimetidine and venlafaxine may be more pronounced in patients on a background of hypertension, liver dysfunction and in the elderly (Caution should be exercised).
There was no interaction between diazepam and its active metabolite dezmetildiazepamom and venlafaxine and its metabolite (EFA) in 18 healthy volunteers in a single dose application of diazepam amid venlafaxine equilibrium conditions.
Receiving a single oral dose of haloperidol on the background venlafaxine equilibrium conditions have 24 healthy volunteers resulted in a change in the pharmacokinetic parameters of haloperidol: decrease in the total clearance of haloperidol 42%, increase AUC by 70% and Cmax on 80%; wherein T1/2 remained unchanged.
A single oral dose of lithium did not affect the pharmacokinetics of venlafaxine (and EFA) at equilibrium at 12 healthy men. Venlafaxine also did not change the pharmacokinetic parameters of lithium.
Venlafaxine is not increased availability of other blood concentration, simultaneously taken drugs with high protein binding (because of the low binding of venlafaxine and EFA to plasma proteins).
Studies in vitro shows, venlafaxine is a weak inhibitor of CYP2D6 isozyme and does not inhibit isozymes CYP3A4, CYP1A2, CYP2C9, CYP2C19.
Venlafaxine has no effect on the pharmacokinetics of imipramine and its active metabolite, imipramine similarly does not affect the pharmacokinetics of venlafaxine and its active metabolite.
A single oral dose of risperidone on a background of venlafaxine under equilibrium conditions was accompanied by an increase in AUC of risperidone on 32% due to a weak inhibition of CYP2D6-mediated metabolism of risperidone to the active metabolite (9-hydroxy-risperidone), wherein the total pharmacological activity (risperidone + metabolite) I have not changed.
In clinical studies revealed no drug interactions with venlafaxine, metabolized with the participation of CYP3A4 (including alprazolam, diazepam, terfenadine).
Receiving a single oral dose of venlafaxine indinavir background in an equilibrium state at 9 healthy volunteers resulted in a decrease in AUC and Cmax of indinavir 28% and 36% respectively (the clinical significance of the identified phenomenon unknown).
A single dose of ethanol (0,5 g / kg) does not influence farmakokinetiku venlafaxine and EFA when taking venlafaxine dose 150 mg / day (in 15 healthy men).
Symptoms: ECG changes (QT prolongation, bundle-branch block, extension of the QRS complex, and others.), sinus and ventricular tachycardia, bradycardia, gipotenziya, dizziness, disturbance of consciousness of varying severity (from drowsiness to coma), convulsions, until death.
Treatment: activated carbon, induction of vomiting, gastric lavage (to reduce the suction). Keeping the airway to ensure adequate ventilation and oxygenation. It is recommended that careful observation and monitoring of cardiac rhythm and other vital functions, symptomatic and supportive therapy. The effectiveness of such measures as the forced diuresis, dialysis, hemoperfusion and exchange transfusion is unlikely. No specific antidote.
In post-marketing studies of venlafaxine overdose cases occurred mostly while taking alcohol and / or other drugs.
Venlafaxine: Dosing and Administration
Inside, simultaneously with the ingestion, the initial dose - 75 mg / day (tablets - The daily dose divided into 2-3 doses, capsules - 1 time / day, at about the same time of day is in the morning or in the evening). For some patients might be desirable starting dose 37,5 mg / day (for 4-7 days). If necessary, may increase the dose (gradually, on 75 mg / day, 1 once every 4 days or more) to 225 mg / day (The recommended dose for depression of moderate severity), hospital (in severe depression) possibly increasing doses up to the maximum — 375 mg / day.
In patients with impaired liver function moderate to severe severity requires reduction of the daily dose in the 50% and more. Against the background of renal dysfunction (speed clubockova filtering is 10-70 mL/min) necessary dose reduction by 25-50%, in hemodialysis — at 50%, the drug should be taken after dialysis. Elderly patients a special dosage adjustments are not required, However, caution should be exercised when treating these patients, especially at higher doses.
The combination with MAO inhibitors
Treatment with venlafaxine should be started no earlier than 14 days after the reception of MAO inhibitors, in turn treated MAO inhibitors can begin no earlier than 7 days after discontinuation of venlafaxine. At simultaneous reception of MAO inhibitors and venlafaxine may develop severe adverse reactions (incl. tremor, myoclonus, profuse sweating, nausea, vomiting, flushing, dizziness; Hyperthermia with signs, similar to neuroleptic malignant syndrome; convulsions, until death).
Some patients develop during treatment resistant venlafaxine-induced hypertension, defined as an increase in diastolic blood pressure in the supine position (Dudley) ≥ 90 mm Hg. Article. and ≥ 10 mm Hg. Article. relative to the base (source) level when measured during three consecutive visits to the doctor.
In premarketingovyh studies when using three fixed doses of venlafaxine- 75, 225 and 375 mg/day in form immediate release tablets versus placebo average value Dudley increase in patients, receiving 375 mg / day, by the end of the 6-th week amounted to 7,2 mm Hg. Art., whereas in the groups of patients, taking doses 75 and 225 mg / day, No significant changes were (in the placebo group decline dADL on 2,2 mm Hg. Art.). Analysis, conducted in patients, meet the criteria of having resistant hypertension, showed a dose-dependent increase in the frequency of its occurrence. At doses of venlafaxine less 100 mg/day resistant hypertension in 3% cases, 101-200 mg/day — 5%, 201-300 mg/day is 7%, more 300 mg/day — 13% (placebo- 2%). Analysis of patients with persistent presence of hypertension and 19 patients, discontinued treatment due to the development of hypertension (less 1% the total number of patients, taking venlafaxine), revealed, that increased to 10 dADL-15 mm Hg. Article. Nevertheless, long-term increase in Dudley may have adverse consequences. Therefore, we recommend regular monitoring of blood pressure in patients, taking venlafaxine. In cases of long-term increase in blood pressure need to either reduce the dose, or decide on the abolition of the drug.
In premarketingovyh trials in patients with major depressive disorder, receiving venlafaxine hydrochloride in the form of The modified-release capsules in doses of 75-375 mg/day 3% cases (19/705) It was marked by persistent hypertension. Patients with generalized anxiety disorder, taking venlafaxine 37.5 doses-225 mg/day, resistant hypertension was observed in 0,5% cases (5/1011). In patients with social phobia, treated with doses of 75-225 mg/day, resistant hypertension was observed in 1,4% cases (4/277). The number of patients in these studies, treated with doses over 300 mg / day, It was insufficient to assess the frequency of blood pressure increase at the highest dose.
Insomnia and nervousness
A pooled analysis of short-term, double-blind, placebo-controlled trials in patients with depression showed, the most common effects, associated with the reception of venlafaxine in the form of immediate release tablets (n=1033) vs placebo (n=609) It was anxiety 6%(3%), nervousness 13%(6%), insomnia 18%(10%), in brackets the percentage placebo. In Phase 2 and Phase 3 Studies in patients with depression, anxiety, nervousness and insomnia led to discontinuation of treatment in 2%, 2% and 3% patients, respectively.
A pooled analysis of short-term studies in patients with depression, generalized anxiety disorder and social phobia showed, the most common effects, associated with the reception of venlafaxine in the form of The modified-release capsules compared with placebo were insomnia and nervousness (in brackets the percentage placebo). Insomnia was observed in 17% cases(11%), nervousness - 10%(5%) patients with a depressive episode (n=357) vs placebo (n=285); 15%(10%) and 6%(4%) in patients with generalized anxiety disorder (n=1381) vs placebo (n=555); 23%(7%) and 11%(3%) in patients with social phobia (n=277) vs placebo (n=274), respectively.
When treating patients with depressive episode 0,9% patients discontinued treatment because of insomnia and 0,9% — due to nervousness. Patients with generalized anxiety disorder in the treatment for up to 8 weeks of insomnia and nervousness caused the cessation of therapy 3 and 2% cases, when the duration of treatment up 6 months-in 2 and 0,7% of cases, respectively. In patients with social phobia in the treatment of up to 12 weeks of insomnia was the cause of the abolition of venlafaxine 3% cases, nervousness was not a cause of drug withdrawal.
Changes in appetite and body weight
According to the results of short-term, double-blind, placebo-controlled trials in patients with depression, the most frequently reported occurring while taking venlafaxine anorexia (11% tablets/8% capsules) vs placebo (2% tablets/4% capsules). Dose-dependent weight loss is often observed in patients, taking venlafaxine for several weeks. A significant decrease in body weight, especially in patients with depression, having too little weight, It may be an undesirable effect of treatment with venlafaxine. The decrease in body weight 5% or more observed on the background of venlafaxine in 6% patients (tablets)/7% (capsules) vs placebo (1%/2%) and 3% patients, taking another antidepressant. Termination of weight loss under the influence of venlafaxine (tablets) rarely mentioned in 0,1% cases in research Phases 2 and Phase 3 in patients with depression. Stopping the progression of anorexia and weight loss in patients with depression at reception capsules There was also a small- 1 and 0,1% respectively.
In short (to 8 Sun) studies in patients with generalized anxiety disorder, receiving venlafaxine in the form of capsules, anorexia was noted in 8% cases (placebo- 2%). The decrease in body weight 7% or more was observed in 3% patients, receiving venlafaxine in the form of capsules for up to 6 Months (placebo- 1%). Termination progression of anorexia and weight reduction when receiving capsules for up to 8 Weeks was observed in 0,9% and 0,3% of patients, respectively.
In studies in patients with social phobia, receiving venlafaxine in the form of capsules for up to 12 Sun, anorexia was noted in 20% cases (Placebo - 2%). The decrease in body weight 7% and is not observed in any patients, receiving venlafaxine in the form of capsules for up to 12 Months, or placebo. Termination progression of anorexia and weight reduction when receiving capsules for up to 12 Weeks was 0,4% and 0,0 % respectively.
Activation of mania / hypomania
A small number of patients with mood disorders, receiving antidepressants, can develop mania or hypomania. According to the results of all tests premarketingovyh venlafaxine in patients with depression mania / hypomania has been featured in 0,5% (tablets) and 0,3% (capsules) cases (placebo 0%). As with other antidepressants, venlafaxine should be used with caution in patients with a history of mania.
It will be appreciated, that against the background of venlafaxine may develop hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone, especially in patients with hypovolemia, dehydration, elderly, and while taking diuretics.
As it reported on the development of venlafaxine in the treatment of mydriasis, you must use it with caution in patients with increased intraocular pressure, or at risk of developing an acute attack of angle-closure glaucoma.
During testing premarketingovyh seizures occurred in 0,26% (8/3082) patients, treated with venlafaxine (tablets), the majority of which (5 from 8) It was observed in patients, taking doses 150 mg / day or less. When receiving venlafaxine in the form of capsules patients with a depressive episode (n=705), generalized anxiety disorder (n=1381) and social phobia (n=277) seizures were observed. Nevertheless, it should be prescribed with care in patients with venlafaxine indication of a history of seizures. With the development of seizures should stop taking the drug.
There are reports on the background of the occurrence of abnormal skin hemorrhages venlafaxine (in most cases, èkhimozov — extensive bleeding into the skin or mucous membranes). The causal relationship of this phenomenon with the reception of venlafaxine is not installed, However, there was a violation of platelet aggregation (possibly due to reduced content of serotonin).
Increased serum cholesterol (cm. Side effects Changes in laboratory parameters) .
When long-term therapy is recommended measurement of serum cholesterol (in clinical trials clinically significant increase in this indicator in patients, treated with venlafaxine).
Due to the possibility of suicide attempts in patients with depression requires careful monitoring of patients in the early treatment and appointment of the minimum effective dose to reduce the risk of overdose. The same caution should be exercised when treating patients with generalized anxiety disorder and social phobia.
Use in patients with concomitant diseases
Clinical experience with venlafaxine in patients in the presence of comorbidities is limited. Care must be taken in a number of diseases and conditions, incl. involving violation of hemodynamics and metabolism (cm. "Restrictions on the use").
There have been no systematic observations in patients with recent myocardial infarction or unstable angina, tk. these patients were excluded from many clinical studies premarketingovyh. However, analysis of the ECG in patients, treated with venlafaxine, shows, that the drug is not associated with the development of clinically significant ECG abnormalities.
Discontinuation of treatment with venlafaxine
It has been reported about the appearance of effects in patients, due to the cessation of venlafaxine treatment (discontinuation effects). In this connection, the abolition of venlafaxine should be gradually, by reducing the dose, to reduce the risk of withdrawal reactions, It is recommended to monitor the patient's condition. Time withdrawal period may depend on the dose, duration of therapy and the individual patient. When treating for venlafaxine 6 weeks or more during the withdrawal of the drug should not be less than 2 Sun.
Manifestations of withdrawal reactions in patients, treated with venlafaxine, We were systematized at a prospective analysis of the results of clinical trials of venlafaxine in generalized anxiety disorder and retrospective review of tests for depression. It has been found, that abrupt discontinuation of venlafaxine or reducing its dose (at various doses) associated with the appearance of symptoms, the frequency of which increases with increasing dose and duration of treatment. Reported symptoms included the following: ažitaciâ, anorexia, alarm, confusion, incoordination, diarrhea, dizziness, dry mouth, disforija, fascicular twitchings, fatiguability, headache, hypomania, insomnia, nausea, nervousness, nightmares, convulsions, violation of the sensitivity (including the sensation of electric shock), drowsiness, Sweating, tremor, vertigo, vomiting.
In conducting clinical trials do not have enough data, pointing, how long you can take venlafaxine in the treatment of depression, generalized anxiety disorder and social phobia.
Although venlafaxine did not enhance the effect of ethanol on psychomotor reaction volunteers, avoid simultaneous reception of venlafaxine and alcohol.
In studies in healthy volunteers had no clinically significant decrease in mental activity and speed of psychomotor reactions against the backdrop of venlafaxine. But, since any psychoactive drug may affect the central nervous system, patients should be warned to use caution when working with potentially dangerous machinery and driving.
|Active substance||Description of interaction|
|Moclobemide||FMR: synergism. Inhibits MAO and the background of venlafaxine provokes the development of adverse reactions, incl. heavy; joint and / or sequential use is contraindicated.|
|Procarbazine||FMR: synergism. Inhibits MAO and the background of venlafaxine provokes the development of adverse reactions, incl. heavy; joint and / or sequential use is contraindicated.|
|Selegiline||FMR: synergism. Inhibits MAO and the background of venlafaxine provokes the development of adverse reactions, incl. heavy; joint and / or sequential use is contraindicated.|