Trade names
Venlafaxine. Efektin. Efektin Depot.
Subgroup
Inhibitors of reverse serotonin and noradrenaline capture.
Action
Pharmacological Effects - antidepressive.
Mechanism of Action
Venlafaxinea antidepressive effect in humans due to increased activity in the CNS NEUROMEDIATOR. In preclinical studies showed that Venlafaxine and its active metabolite - O-dezmetilVenlafaxine (ODV) are powerful inhibitors of reverse neuronal capture of serotonin and norepinephrine, and weak inhibitors of reverse capture dofamina. Venlafaxine and EFA in vitro had no significant affinity to muskarinovym, gistaminergicheskim, alfa1-adrenergic receptors, did not have the ability to inhibit MAO.
Pharmacokinetics
After ingestion Venlafaxine well absorbed and extensively metabolized in the liver. After receiving the single dose is absorbed by at least 92%, absolute bioavailability is approximately 45% (due presistemnogo metabolism). Eating does not have a significant influence on the absorption and biotransformation Venlafaxinea.
Metabolized primarily to the formation of a single pharmacologically active metabolite (EFA), as well as a number of inactive - N-dezmetilVenlafaxine, N, O-didezmetilVenlafaxine etc.
Equilibrium concentrations in plasma as Venlafaxinea, and EFA is achieved within 3 days of repeated admission. Pharmacokinetics Venlafaxinea and EFA is linear in the range of daily doses of 75-450 mg / day (while taking every 8 h). Plasma clearance, T1 / 2 and volume of distribution in the equilibrium condition was unchanged for Venlafaxinea, and for the EFA, after receiving multiple doses. In the equilibrium state of the plasma clearance Venlafaxinea and EFA was 1,3 ± 0,6 l / h / kg and 0,4 ± 0,2 l / h / kg, T1 / 2 - 5 ± 2 h and 11 ± 2 h, the volume distribution - 7,5 ± 3,7 l / kg and 5,7 ± 1,8 l / kg, respectively.
Derive predominantly kidney: about 87% of dose derived from the urine within 48 h (5% - unchanged, 29% - in the form of nekonyugirovannogo EFA, 26% - in the form of conjugated EFA, 27% - in other inactive metabolites).
Indications
Venlafaxinea hydrochloride in the form of tablets with immediate release is indicated for the treatment of depression.
Venlafaxinea hydrochloride in the form of modified release capsules is indicated for the treatment of depression, generalized anxiety disorder and social phobias.
Contraindications
Hypersensitivity, simultaneously receiving MAO inhibitors.
Limitations to the use of
Recently transferred myocardial infarction and unstable angina, changes in blood pressure, increased intraocular pressure and glaucoma zakrytougolnaya, manic state in history, the initially low body weight, kidney / liver failure, up to age 18 (safety and efficacy of the application is not installed).
Side Effects
The most frequent side effects while taking Venlafaxinea hydrochloride were asthenia, sweating, nausea, constipation, anorexia, vomiting, drowsiness, dry mouth, dizziness, nervousness, anxiety, tremors, lack of clarity of view, the violation of ejaculation / orgasm and impotence in men.
The most common effects associated with receiving Venlafaxinea in the form of capsules with a modified release, were insomniya and nervousness.
Dependence syndrome and the abolition of
It was found that the sharp Venlafaxinea stopping or reducing its dose (at different doses) associated with the appearance of symptoms, the frequency of which increased with increasing dose and duration of treatment. Reported symptoms included the following: agitation, anorexia, anxiety, confusion, violation of coordination, diarrhea, dizziness, dry mouth, dysphoria, fastsikulyarnye jumps, fatigue, headache, gipomaniya, insomniya, nausea, nervousness, nightmares, convulsions, a violation of the sensitivity (including a feeling of shock electrocution), drowsiness, sweating, tremor, vertigo, vomiting.
In this regard, the abolition of Venlafaxinea should be carried out gradually, by reducing the dose to reduce the risk of reactions cancel, you are advised to monitor the condition of the patient. The time period may depend on the lifting of dose, duration of therapy and individual characteristics of the patient. When treating Venlafaxineom for 6 weeks or more during the lifting of the drug must be at least 2 weeks.
Interaction
Incompatible with MAO inhibitors. Venlafaxineom treatment should start no earlier than 14 days after receiving MAO inhibitors, in turn, treated MAO inhibitors can be started no earlier than 7 days after the lifting Venlafaxinea. If you are receiving Venlafaxinea and MAO inhibitors may develop severe adverse reactions (including tremor, mioklonus, copious sweating, nausea, vomiting, flush-to-face, dizziness, hyperthermia with features similar to neyrolepticheskim malignant syndrome, seizures, up to death).
Dosing and Administration in Adults
Inside, along with the eating, the starting dose - 75 mg / day (tablets - daily dose is divided into 2-3 reception capsules - 1 times / day, approximately at the same time of day - morning or evening). For some patients it may be desirable starting dose of 37.5 mg / day (within 4-7 days). If necessary, possibly increasing dose (slowly, at 75 mg / day, 1 every 4 days or more) to 225 mg / day (the recommended dose, with an average degree of severity of depression), in the hospital (in severe depression) may increase dose to the maximum -- 375 mg / day.
In patients with liver dysfunction of moderate and severe degree of reduction of required daily intake of 50% or more. Against the background of violations of kidney function (glomerular filtration rate - 10-70 ml / min) needed dose reduction to 25-50%, with dialysis - at 50%, the drug should be taken after dialysis. Patients older special dose adjustment is required, but care should be taken in treating this category of patients, especially with increasing dose.
Dosing and Administration in pediatric practice
In the age of 18 safety and efficacy of the application is not installed.
Pregnancy and lactation
If pregnancy can only use when absolutely necessary (adequate and strictly controlled studies safety of pregnant women are not held).
Venlafaxine and its active metabolite EFA penetrate the breast milk of women. Given the potential risk of serious side effects in children who are breastfed, breastfeeding women should stop or breastfeeding, or drug treatment.
Overdosage
Symptoms: ECG changes (prolongation of interval QT, block feet beam Gisa, the expansion of QRS complex, etc.), sinus and ventricular tachycardia, bradycardia, hypotension, dizziness, mental blankness of varying degrees of expression (from drowsiness to coma), convulsions, until the fatal outcome.
Treatment: the use of activated charcoal, induction of vomiting, gastric lavage (to reduce absorption). Maintain adequate airway to ensure adequate ventilation and oxygenation. We recommend close observation and monitoring of heart rate and other vital signs, symptomatic and supportive therapy. The effectiveness of such measures as forced diuresis, dialysis, gemoperfuziya and exchange blood transfusions is unlikely. No specific antidote. In cases of overdose postmarketingovyh studies were mainly Venlafaxinea while receiving alcohol and / or other drugs.
Cautions
It should be noted that against the backdrop of Venlafaxinea may develop hyponatremia and syndrome of inappropriate secretion antidiureticheskogo hormone, especially in patients with hypovolemia, dehydration in the elderly, as well as while receiving diuretics.
As reported on developments in the treatment of midriaza Venlafaxineom, you must use them with caution in patients with elevated intraocular pressure or risk of an acute attack of glaucoma zakrytougolnoy.
Although Venlafaxine do not increase the impact of ethanol on psychomotor reaction from volunteers, should be avoided while receiving Venlafaxinea and alcohol.
In studies on healthy volunteers has not been observed clinically meaningful reduction of thinking and psychomotor speed of reaction on the background Venlafaxinea. However, since any psychoactive drug may affect the CNS, patients should be warned of the need to observe caution when working with potentially dangerous machinery and when driving a car.
