Description of the active substance:
This information is a reference and it is not enough that the drug was prescribed by a doctor. .
PHARMACHOLOGIC EFFECT
Antidepressant. On the chemical structure of venlafaxine can not be attributed to any known class of antidepressants (tricyclic, tetracyclic or other). It has two active enantiomeric racemic forms.
The antidepressant effect of venlafaxine is associated with an increase in neurotransmitter activity in the CNS. Venlafaxine and its basic metabolite O-desmethylvenlafaxine (EFA) are potent inhibitors of the reuptake of serotonin and noradrenaline and slightly inhibit the reuptake of dopamine by neurons. Venlafaxine and EFA equally effectively affect the reuptake of neurotransmitters. Venlafaxine and EFA reduce beta-adrenergic reactions.
Venlafaxine does not have an affinity for m- and n-holinoretseptora, histamine H 1 -receptors and? 1- adrenoreceptors of the brain. Venlafaxine does not suppress MAO activity. Has no affinity for opioid, benzodiazepine, phencyclidine or NMDA receptors.
PHARMACOKINETICS
After ingestion, venlafaxine is well absorbed from the digestive tract. After a single dose in doses of 25-150 mg C max in blood plasma is achieved within approximately 2.4 hours and is 33-172 ng / ml. Venlafaxine undergoes intensive metabolism during "first passage" through the liver. C max EFA in blood plasma is reached approximately 4.3 hours after administration and is 61-325 ng / ml. In the range of daily doses of 75-450 mg venlafaxine and EFA have linear kinetics. After intake during meals, the time to reach Cmax in blood plasma is increased by 20-30 min, but the C max and absorption values ​​do not change.
The binding of venlafaxine and EFA to plasma proteins is 27% and 30%, respectively. With repeated administration of C ss venlafaxine and EFA are achieved within 3 days.
The main metabolite is EFA. T 1/2 venlafaxine and EFA is 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, venlafaxine and EFA plasma concentrations are elevated, and the rate of their elimination is reduced. With moderate or severe renal failure, the total clearance of venlafaxine and EFA is reduced, and T 1/2 is lengthened. The decrease in overall clearance is mainly observed in patients with QC less than 30 ml / min. Age and sex of the patient do not affect the pharmacokinetics of venlafaxine.
INDICATIONS
Depression of various etiologies (treatment and prevention).
DOSING MODE
Is taken internally. The recommended initial dose is 75 mg in 2 divided doses (37.5 mg 2 times / day) daily. If after several weeks of treatment there is no significant improvement, the daily dose can be increased to 150 mg (75 mg 2 times / day). In severe depression or other conditions requiring in-patient treatment, 150 mg can be used immediately in 2 divided doses (75 mg 2 times / day). After this, the daily dose can be increased by 75 mg every 2-3 days until the desired therapeutic effect is achieved. The maximum dose is 375 mg / day.
After achieving the necessary therapeutic effect, the daily dose can be gradually reduced to a minimum effective level. The length of the period necessary to reduce the dose depends on the size of the dose, the duration of therapy, and the individual sensitivity of the patient.
For maintenance therapy and prevention of relapses, the minimum effective dose used in the treatment of a depressive episode is shown.
Patients with renal insufficiency with CC 10-30 ml / min dose should be reduced by 25-50%. In connection with the elongation of T 1/2 of venlafaxine and its active metabolite (EFA), such patients should take the entire dose 1 time / day.
Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after the completion of the hemodialysis session.
With moderate hepatic insufficiency (prothrombin time from 14 to 18 sec), the dose should be reduced by 50%.
In elderly patients, venlafaxine should be used at the lowest effective dose. When the dose is raised, the patient should be under careful medical supervision.
At the end of treatment, it is recommended that the dose be gradually reduced, at least within a week, and monitored by the patient to minimize the risk associated with cancellation of venlafaxine. The length of the period necessary to reduce the dose depends on the size of the dose, the duration of therapy, and the individual sensitivity of the patient.
SIDE EFFECT
Most side effects depend on the dose. With long-term treatment, the severity and frequency of most of these effects is reduced, and there is no need to cancel therapy.
On the part of the digestive system: decreased appetite, constipation, nausea, vomiting, dry mouth; rarely - hepatitis.
From the side of metabolism: increased serum cholesterol levels, weight loss; sometimes - a violation of functional liver tests, hyponatremia, a syndrome of insufficient secretion of ADH.
From the side of the cardiovascular system: arterial hypertension, hyperemia of the skin; sometimes - postural hypotension, tachycardia.
From the side of the central nervous system and peripheral nervous system: unusual dreams, dizziness, insomnia, nervous excitability, paresthesia, stupor, increased muscle tone, tremor, yawning; sometimes - apathy, hallucinations, muscle spasms, serotonergic syndrome; rarely - epileptic seizures, manic reactions, as well as symptoms reminiscent of the NSA.
From the side of the urinary system: dysuria (mainly - difficulty in the beginning of urination); sometimes - retention of urine.
On the part of the reproductive system: violations of ejaculation, erections, anorgasmia; sometimes - a decrease in libido, menorrhagia.
From the sense organs: disorders of accommodation, mydriasis, visual impairment; sometimes - a violation of taste sensations.
Dermatological reactions: sweating; sometimes - photosensitivity.
From the hemopoietic system: sometimes - hemorrhages in the skin (ecchymoses) and mucous membranes, thrombocytopenia; rarely - prolonged bleeding time.
Allergic reactions: sometimes - skin rash; rarely - erythema multiforme, Stevens-Johnson syndrome; very rarely - anaphylactic reactions.
Other: weakness, fatigue.
After a sharp cancellation or reduction in the dose , fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, anxiety, nervous irritability, disorientation, hypomania, paresthesia, sweating are possible. These symptoms are usually mild and go untreated.
CONTRAINDICATIONS
Renal failure of severe degree (CC <10 ml / min); severe violations of liver function; simultaneous administration of MAO inhibitors; children and adolescents under 18; established or suspected pregnancy; lactation period (breastfeeding); increased sensitivity to venlafaxine.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation (breastfeeding).
Women of childbearing age should apply reliable methods of contraception during the treatment period and immediately consult a doctor in case of pregnancy or pregnancy planning.
Venlafaxine and the metabolite of EFA are excreted in breast milk. The safety of these substances for newborn babies is not proven, therefore, if necessary, taking venlafaxine during lactation should resolve the issue of stopping breastfeeding. If the mother's treatment was completed shortly before the birth, the newborn can experience withdrawal symptoms.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in renal failure of severe degree (CC <10 ml / min).
Patients with renal insufficiency with CC 10-30 ml / min dose should be reduced by 25-50%. In connection with the elongation of T 1/2 of venlafaxine and its active metabolite (EFA), such patients should take the entire dose 1 time / day.
Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after the completion of the hemodialysis session.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe violations of liver function.
With moderate hepatic insufficiency (prothrombin time from 14 to 18 sec), the dose should be reduced by 50%.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
In elderly patients, venlafaxine should be used at the lowest effective dose. When the dose is raised, the patient must be under careful medical supervision
Elderly patients should be warned about the possibility of dizziness and discomfort. During the administration of venlafaxine, especially in conditions of dehydration or a decrease in BCC, elderly patients may experience hyponatremia and / or ADH deficiency syndrome
SPECIAL INSTRUCTIONS
Caution should be used venlafaxine after a recent myocardial infarction, with heart failure in the stage of decompensation, with unstable angina, arterial hypertension, tachycardia, tachyarrhythmias, history of convulsions, intraocular hypertension, angle-closure glaucoma, manic conditions in the anamnesis, a predisposition to bleeding from the skin covers and mucous membranes, initially reduced body weight.
In patients with depressive disorders, the likelihood of suicidal attempts should be considered before initiating any drug therapy. Therefore, to reduce the risk of overdose at the beginning of treatment, whenever possible, venlafaxine should be used at the lowest effective dose, and the patient should be under close medical supervision.
In patients with affective disorders in the treatment of antidepressants (including venlafaxine), hypomanic or manic conditions may occur. Like other antidepressants, venlafaxine should be administered with caution to patients with a history of mania. Such patients need medical supervision.
If epileptic seizures occur, treatment should be discontinued.
The risk of tachycardia increases with venlafaxine in high doses.
During treatment, regular monitoring of blood pressure is recommended, especially during the period of refining or increasing the dose.
Patients, especially the elderly, should be warned about the possibility of dizziness and discomfort.
During the administration of venlafaxine, especially in conditions of dehydration or reduction of BCC (including in elderly patients and patients taking diuretics), hyponatremia and / or ADH deficiency syndrome may occur.
During the administration of the drug may be observed mydriasis, in connection with which it is recommended to control intraocular pressure in patients prone to its increase or suffering from an angle-closure glaucoma.
As with other drugs acting on the central nervous system, the physician should establish careful monitoring of patients to identify signs of abuse of venlafaxine.Careful monitoring and follow-up are necessary for patients who have a history of such symptoms.
On the background of taking venlafaxine, special care should be taken when conducting electroconvulsive therapy, experience with venlafaxine in these conditions is absent.
During the treatment should avoid drinking alcohol.
Impact on the ability to drive vehicles and manage mechanisms
Despite the fact that venlafaxine does not affect psychomotor and cognitive functions, it should be taken into account that any drug therapy with psychoactive drugs can worsen thinking processes and reduce the ability to perform motor functions. This should be warned by the patient before starting treatment. If such violations occur, the extent and duration of the restrictions should be determined by the physician.
DRUG INTERACTION
Venlafaxine can be taken 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 h). Therapy with MAO inhibitors can begin at least 7 days after the withdrawal of venlafaxine.
The simultaneous use of venlafaxine with lithium can increase the concentration of the latter in blood plasma.
It is possible to enhance the effects of haloperidol due to an increase in its concentration in the blood when combined with venlafaxine.
With simultaneous use with clozapine, there may be an increase in its level in the blood plasma and the development of side effects (eg, epileptic seizures).
The main way to eliminate venlafaxine involves metabolism involving CYP2D6 and CYP3A4, therefore, special care should be taken when administering venlafaxine in combination with drugs that are inhibitors of these two enzymes. The nature of this interaction has not yet been studied.
Cimetidine suppresses the metabolism of venlafaxine in the "first pass" 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 in liver failure).
With simultaneous administration with warfarin, the anticoagulant effect of the latter can be enhanced.
