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Active ingredients
Venlafaxine
Release form
Pills
Composition
Venlafaxine (in the form of hydrochloride) 37.5 mg. Excipients: lactose monohydrate - 84.93 mg, microcrystalline cellulose - 36 mg, sodium starch glycolate (type A) - 12.6 mg, anhydrous colloidal silicon dioxide - 1.35 mg, magnesium stearate - 2.7 mg.
Pharmacological effect
Antidepressant. The chemical structure of venlafaxine cannot be attributed to any known class of antidepressants (tricyclic, tetracyclic, or others). It is the racemate of two active enantiomers .; The mechanism of antidepressant action 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 inhibitors of serotonin and noradrenaline reuptake and weak inhibitors of dopamine reuptake. In addition, venlafaxine and EFA reduce beta-adrenergic activity, both after a single injection, and with constant admission. Venlafaxine and EFA equally effectively affect the reuptake of neurotransmitters .; Venlafaxine has no affinity for the m- and n-cholinergic receptors, histamine H1 receptors and 1-adrenergic receptors of the brain. Venlafaxine does not inhibit the activity of MAO. It has no affinity for opioid, benzodiazepine, phencyclidine or NMDA receptors.
Pharmacokinetics
Absorption; After oral administration, venlafaxine is well absorbed from the gastrointestinal tract. After a single dose in doses of 25-150 mg Cmax in plasma, it is reached within about 2.4 hours and is 33-172 ng / ml. Venlafaxine is extensively metabolized during the "first pass" through the liver .; Cmax EFA in plasma is reached approximately 4.3 hours after administration and amounts to 61-325 ng / ml .; In the range of daily doses of 75-450 mg, venlafaxine and EFA have linear kinetics. After taking the drug while eating, the time to reach Cmax in the blood plasma is increased by 20-30 minutes, but the values of Cmax and absorption do not change .; Distribution; The binding of venlafaxine and EFA to plasma proteins is 27% and 30%, respectively; With repeated intake of Css, venlafaxine and EFA are achieved within 3 days .; Metabolism and excretion; The main metabolite is O-desmethylvenlafaxine (EFA) .; T1 / 2 venlafaxine and EFA is 5 and 11 hours respectively; EFA and other metabolitesas well as unchanged venlafaxine excreted by the kidneys .; Pharmacokinetics in special clinical situations; In patients with liver cirrhosis, plasma plasma concentrations of venlafaxine and EFA are increased, and their elimination rate is reduced .; With moderate or severe renal failure, the total clearance of venlafaxine and EFA decreases, and T1 / 2 is prolonged. A decrease in total clearance is mainly observed in patients with glomerular filtration rate (GFR) of less than 30 ml / min; The age and sex of the patient do not affect the pharmacokinetics of the drug.
Indications
Depression of various etiologies (treatment and prevention).
Contraindications
Severe renal dysfunction (creatinine clearance less than 10 ml / min). Severe abnormal liver function. ; Simultaneous administration of MAO inhibitors. ; Children and adolescents up to 18 years (safety and efficacy for this category of patients has not been proven). ; Established or suspected pregnancy. ; Lactation period (breastfeeding). ; Hypersensitivity to the drug. ; The drug should be prescribed with caution in the following cases: A recent myocardial infarction. ; Unstable angina. ;Arterial hypertension. ;Tachycardia. ; Convulsions in history. ; Intraocular hypertension. ; Angle-angle glaucoma. ; Manic history in history. ; Predisposition to bleeding from the skin and mucous membranes. ; Initially reduced body weight.
Use during pregnancy and lactation
The safety of the drug Velaxin; during pregnancy is not proven. Therefore, use during pregnancy (or intended pregnancy) is possible only if the intended benefit to the mother outweighs the possible risk to the fetus .; Women of childbearing age should apply reliable methods of contraception during the period of drug treatment and immediately consult a doctor in the event of pregnancy or pregnancy planning .; Venlafaxine and the EFA metabolite are excreted in breast milk. The safety of these substances for newborns is not proven, so if you need to take the drug during lactation, you should decide on the termination of breastfeeding. If the mother’s treatment was completed shortly before delivery, the newborn may experience withdrawal symptoms.
Dosage and administration
Velexin pills are recommended to be taken with meals. ; The recommended initial dose is 75 mg in 2 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). If, in the opinion of the doctor, a higher dose is necessary (severe depressive disorder or other conditions requiring inpatient treatment), 150 mg can be prescribed immediately in 2 doses (75 mg 2 times / day). After that, 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 the drug Velaxin is 375 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level. The duration of the period required to reduce the dose depends on the dose, the duration of therapy, as well as the individual sensitivity of the patient. ; At the end of the administration of Velaxin, it is recommended to gradually reduce the dosage of the drug, at least during the week, and monitor the patient's condition in order to minimize the risk associated with discontinuation of the drug. The duration of the period required to reduce the dose depends on the dose, the duration of therapy, as well as the individual sensitivity of the patient. ; Supportive care and relapse prevention .; Maintenance therapy may last 6 months or more. The drug is prescribed in the minimum effective doses used in the treatment of a depressive episode. ; Use in violation of liver function: In case of mild hepatic insufficiency (prothrombin time less than 14 sec), the dosage regimen is not required to be adjusted. In moderate liver failure (prothrombin time from 14 to 18 seconds), the dose should be reduced by 50%. It is not recommended to use venlafaxine in case of severe hepatic insufficiency, since there are no reliable data on the safety of such therapy. ; Use in violation of kidney function: In case of renal insufficiency of mild severity (creatinine clearance (QC) of more than 30 ml / min), no dosage regimen correction is required. In case of moderate renal failure (CC 10-30 ml / min), the dose should be reduced by 25-50%.In connection with the lengthening of T 1/2 of venlafaxine and its active metabolite (EFA), such patients should take the entire dose 1 time / day. Venlafaxine is not recommended for severe renal failure (CC less than 10 ml / min), as there are no reliable data on the safety of such therapy. ; Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completing a hemodialysis session. ; Use in elderly patients: In elderly patients, the drug should be used with caution in connection with the possibility of impaired renal function. The smallest effective dose should be applied. At higher doses, the patient must be under close medical supervision.
Side effects
Most side effects are dose dependent. With prolonged treatment, the severity and frequency of most of these effects is reduced, and there is no need to cancel therapy. ; After abrupt withdrawal of Velaxin or dose reduction, fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, nervous irritability, disorientation, hypomania, paresthesia, sweating are possible. 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 it in high doses. ; On the part of the digestive system: loss of appetite, constipation, nausea, vomiting, dry mouth. Rarely - hepatitis. ; From the exchange of substances: an increase in serum cholesterol, weight loss. Infrequently - a violation of functional liver samples, hyponatremia, syndrome of insufficient secretion of ADH. ; Since the cardiovascular system: hypertension, hyperemia of the skin. Infrequently - postural hypotension, tachycardia. ; From the side of the central nervous system and peripheral nervous system: unusual dreams, dizziness, insomnia, nervous irritability, paresthesias, stupor, increased muscle tone, tremor, yawning. Infrequently - apathy, hallucinations, muscle spasms, serotonergic syndrome. Rarely - epileptic seizures, manic reactions, as well as symptoms resembling neuroleptic malignant syndrome.; From the urinary system: dysuria (mainly - difficulty at the beginning of urination). Infrequently - urine retention. ; On the part of the reproductive system: impaired ejaculation, erection, anorgasmia. Infrequently - decrease in a libido, menorrhagia. ; From the sense organs: accommodation disturbances, mydriasis, visual disturbances. Infrequently - a violation of taste. ; Dermatological reactions: sweating. Infrequently - photosensitivity. ; From the hemopoietic system: infrequently - hemorrhages into the skin (ecchymosis) and mucous membranes, thrombocytopenia. Rarely - lengthening bleeding time. ; Allergic reactions: rarely - skin rash. Rarely - erythema multiforme, Stevens-Johnson syndrome. Very rarely - anaphylactic reactions. ; Other: weakness, fatigue.
Overdose
Symptoms: ECG changes (lengthening of the QT interval, blockade of the bundle of the His, extension of the QRS complex), sinus or ventricular tachycardia, bradycardia, hypotension, convulsive states, change of consciousness (decreased wakefulness). With an overdose of venlafaxine while taking it with alcohol and / or other psychotropic drugs, death was reported .; Treatment: symptomatic treatment. Specific antidotes are unknown. Continuous monitoring of vital functions (respiration and circulation) is recommended. The appointment of activated carbon to reduce the absorption of the drug. Do not induce vomiting due to the risk of aspiration. Venlafaxine and EFA are not displayed during dialysis.
Interaction with other drugs
The simultaneous use of Velaxin with MAO inhibitors is contraindicated. Use of the drug Velaxin; You can start at least 14 days after the end of therapy with MAO inhibitors. If a reversible MAO inhibitor (moccobemide) was used, this interval may be shorter (24 hours). Therapy with MAO inhibitors can begin no less than 7 days after discontinuation of the drug Velaxin; Venlafaxine does not affect the pharmacokinetics of lithium .; With simultaneous use with imipramine, the pharmacokinetics of venlafaxine and its EFA metabolite do not change .; It is possible to enhance the effects of haloperidol due to an increase in its concentration in the blood when combined with Velaksinom .; With simultaneous use with diazepam pharmacokinetics of drugs and their major metabolites are not significantly changed.Also, no effect on the psychomotor and psychometric effects of diazepam was found .; With simultaneous use with clozapine, an increase in its blood plasma level and the development of side effects (for example, epileptic seizures) may be observed .; With simultaneous use with risperidone (despite an increase in the AUC of risperidone), the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) did not change significantly .; Enhances the effect of ethanol on psychomotor reactions .; Metabolism of venlafaxine with the formation of the active metabolite EFA occurs with the participation of the CYP2D6 isoenzyme. Unlike many other antidepressants, the dose of venlafaxine can not be reduced while used with CYP2D6 inhibitors, or in patients with a genetically determined decrease in CYP2D6 activity, since the total concentration of the active substance and metabolite (venlafaxine and EFA) does not change .; The main route of elimination of venlafaxine involves metabolism involving CYP2D6 and CYP3A4, therefore special care should be taken when prescribing venlafaxine in combination with drugs that are inhibitors of these two enzymes. The nature of this interaction has not yet been studied .; Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not inhibit the activity of CYP1A2, CYP2C9, and CYP3A4 isoenzymes; therefore, one should not expect its interaction with other drugs, in the metabolism of which these liver enzymes are involved .; Cimetidine inhibits venlafaxine metabolism during the "first pass" through the liver and does not affect the pharmacokinetics of EFA. In the majority of patients, only a slight increase in the total pharmacological activity of venlafaxine and EFA is expected (more pronounced in elderly patients and in violation of the function of the liver) .; No clinically significant interaction of venlafaxine with antihypertensive drugs (including beta-blockers, ACE inhibitors and diuretics) and hypoglycemic drugs was found; Since the binding of plasma proteins venlafaxine and EFA is, respectively, 27% and 30%, no drug interaction due to impaired binding to plasma proteins is assumed; .; When taken simultaneously with warfarin, the anticoagulant effect of the latter may be enhanced. When taken simultaneously with indinavir, there is a decrease in AUC of indinavir by 28% and a decrease in its Cmax by 36%, while the pharmacokinetic parameters of venlafaxine and EFA do not change. The clinical significance of this effect is unknown.
special instructions
Abrupt cessation of therapy with Velaxine (as well as other antidepressants), especially after use in high doses, can cause withdrawal symptoms, and therefore it is recommended to gradually reduce its dose before discontinuation of the drug. The duration of the period required to reduce the dose depends on the dose, the duration of therapy, as well as the individual sensitivity of the patient .; In patients with depressive disorders, the likelihood of suicidal attempts should be considered before starting any drug therapy. Therefore, to reduce the risk of overdose at the beginning of treatment, the drug should, if possible, be used in the minimum effective dose, and the patient should be under close medical supervision .; Patients with affective disorders in the treatment of antidepressants (including venlafaxine) may experience hypomania or mania. Like other antidepressants, venlafaxine should be used with caution in patients with a history of mania. Such patients need medical supervision .; Velaxin; (like other antidepressants) should be prescribed with caution in patients with a history of epileptic seizures. Treatment with venlafaxine should be interrupted when epileptic seizures occur .; Patients should be warned of the need to immediately consult a doctor if they develop a rash, urticaria, or other allergic reactions .; In some patients, a dose-dependent increase in blood pressure was observed during the use of venlafaxine, therefore, regular monitoring of blood pressure is recommended, especially during the period of clarification or increase in dose .; It is recommended to use the drug with caution in patients with tachyarrhythmia. During treatment with a drug, an increase in heart rate is possible, especially while taking it in high doses .; Patients, especially the elderly, should be warned about the possibility of dizziness and imbalance .; Like other serotonin reuptake inhibitors, venlafaxine may increase the risk of hemorrhages in the skin and mucous membranes. When treating patients prone to such conditions, caution is needed. During the application of venlafaxine, especially in conditions of dehydration or reduction of the BCC (includingin elderly patients and patients taking diuretics), hyponatremia and / or syndrome of insufficient secretion of ADH may be observed .; During the use of the drug, mydriasis can be observed, and therefore it is recommended to control intraocular pressure in patients who are prone to its increase or suffer from angle-closure glaucoma .; Caution should be given to Velaxin; patients who have recently had a myocardial infarction and suffer from decompensated heart failure, since the safety of the drug in this category of patients has not been studied .; Conducted to date, clinical trials have not revealed tolerance to venlafaxine or dependence on it. Despite this, as with the treatment of other drugs acting on the central nervous system, the doctor should establish careful monitoring of patients to identify signs of drug abuse. Careful monitoring and observation is necessary for patients with a history of indicating such symptoms .; When prescribing the drug Velaxin; patients with lactose intolerance should consider the lactose content (84.93 mg in each tablet 37.5 mg; 169.86 mg in each tablet 75 mg) .; While taking venlafaxine, special care should be taken when conducting electroconvulsive therapy, since experience with venlafaxine in these conditions is absent .; During the period of treatment with the drug Velaxin; alcohol should be avoided .; Use in pediatrics; Safety and efficacy of the drug in children and adolescents under the age of 18 years have not been studied .; Influencing the ability to drive vehicles and control mechanisms; Although venlafaxine does not affect psychomotor and cognitive functions, it should be borne in mind that any drug therapy with psychoactive drugs may reduce the ability to make judgments, thinking or performing motor functions. This should alert the patient before starting treatment. When such violations occur, the degree and duration of the restrictions must be established by the doctor.